Bharat Biotech COVID-19 vaccine

Extended version of the vaccine

Alternative names:
Covaxin; BBV152

Authorization

World Health Organization Emergency Use Listing Procedure

Listed for emergency use on 3 November 2021 [WHO, 2021 ].
Suspension of supply [WHO, 2022 ]

EUL/WHO Authorization: Authorized for emergency use in individuals 18 years of age and older [WHO, 2021 ].
SAGE/WHO Recommendation: Recommended for individuals 18 years of age and older [WHO, 2022 ].

European Commission (based upon the recommendation of the European Medicines Agency [EMA])
Not authorized.

Central Drugs Standard Control Organization (CDSCO, India)
Authorized on 3 January 2021 [Ministry of Health and Family Welfare. Government of India, 2021 ].
Conditional marketing authorization for individuals 18 years of age and older.

Regulatory Authorities of Regional Reference in the Americas

National Administration of Drugs, Foods and Medical Devices (ANMAT, Argentina)
Not authorized.

Brazilian Health Regulatory Agency (ANVISA, Brazil)
Authorization suspended.

Health Canada
Not authorized.

Public Health Institute (ISP, Chile)
Not authorized.

National Institute of Food and Drug Monitoring (INVIMA, Colombia)
Not authorized.

Center for the State Control of Drug Quality (CECMED, Cuba)
Not authorized.

U.S. Food and Drug Administration (FDA)
Not authorized.

Federal Commission for the Protection against Sanitary Risk (COFEPRIS, Mexico)
Authorized for emergency use on 6 April 2021 [COFREPRIS, 2021 ].

Authorization in jurisdictions in Latin America and the Caribbean
Guyana
Paraguay
Peru
Trinidad and Tobago

Authorization in other jurisdictions
Bahrain
Botswana
Comoros
Ethiopia
Iran
Malaysia
Mauritius
Nepal
Oman
Philippines
Vietnam
Zimbabwe

The Emergency Use Authorization does not constitute marketing authorization in the country.

Manufacturing

Manufacturer
Bharat Biotech, India: Bharat Biotech COVID-19 vaccine from India was developed in collaboration with the Indian Council for Medical Research (ICMR) and the National Institute of Virology (NIV).

Other manufacturers
Indian Immunologicals Ltd (IIL), located in India, produces the Covaxin drug substance for supplying Bharat Biotech to accelerate production.

Haffkine Biopharmaceutical Corporation, India. Manufacturer of the vaccine.

Ocugen Inc, USA. Partnered with Bharat Biotech to co-develop the COVID-19 vaccine candidate for the U.S. market.

General characteristics

The Bharat Biotech COVID-19 vaccine (BBV152) is a whole virion inactivated SARS-CoV-2 antigen adsorbed to alum and formulated with a toll-like receptor (TLR) 7/8 agonist Imidazo quinolin gallamide (IMDG) and the preservative 2-phenoxyethanol [WHO, 2022 ].

The Bharat Biotech COVID-19 vaccine is given in 2 doses, separated by 4 weeks. Inactivated vaccines have been used for diseases such as seasonal influenza, polio, and hepatitis A. Inactivated vaccines cannot replicate and therefore cannot infect individuals. IMDG and alum are adjuvants added to enhance immunogenicity. IMDG is a novel adjuvant which has not been used in any previous vaccine [WHO, 2022 ].

Studies generally demonstrate that TLR 7/8 agonists enhance Th1 responses and inhibit Th2 responses which is considered beneficial for COVID-19 vaccines. In addition, CD8 T-cell responses may be increased when using TLR 7/8 agonists as adjuvants [Ganneru B, 2021 ].

Ingredients

The vaccine contains the following ingredients:

Active ingredient

6µg of whole-virion inactivated SARS-CoV-2 antigen (Strain: NIV-2020-770).

Excipients

250 µg of aluminum hydroxide gel.
15 µg of TLR 7/8 (imidazoquinolinone)
2.5 mg of 2-phenoxyethanol.
0.5 mL of phosphate buffer saline.

Risk considerations

Purified inactivated viruses have been traditionally used for vaccine development and such vaccines have been found to be safe and effective for the prevention of diseases caused by viruses like influenza and poliovirus [Gao Q, 2020 ].

Studies performed in mouse models on SARS-CoV and MERS-CoV showed that animals exposed to whole inactivated vaccines exhibited an immunopathologic-type lung disease. [Tseng CT, 2012 ]. This condition would be probably caused by a response from type 2 (Th2) helper T cells. Although the cellular response can be elicited by many vaccines, protection against subsequent coronavirus infections is largely mediated for humoral immunity. The 'cytokine storm' induced by excess T cells has been shown to accentuate the pathogenesis of COVID-19 [Qiang Gao, 2020 ].

Dosing and schedule

The Bharat Biotech COVID-19 vaccine is administered as a series of two doses (0.5 mL each). According to the manufacturer’s product label, the vaccine can be administered with an interval of 4 weeks [WHO, 2022 ].

The pharmaceutical form is a suspension for intramuscular injection that is provided as a monodose vial of 0.5 mL or, as a multidose vial of 5, 10 and 20 doses [WHO, 2021 ].
The preferred site of injection is the deltoid muscle of the upper arm.

If administration of the second dose is inadvertently delayed beyond 4 weeks, it should be given as soon as possible.

Booster dose [WHO, 2022 ]
A booster dose is recommended for the highest and high priority-use groups (i.e. older adults, health workers, persons with comorbidities), administered 4–6 months after completion of the primary series.

Once high booster dose coverage has been achieved in the highest priority-use group, countries may also consider a booster for other lower priority-use groups.

If more than 6 months have elapsed since completion of the primary series, a booster dose should be given at the earliest opportunity.

Heterologous schedule [WHO, 2022 ]
WHO supports a flexible approach to using different EUL COVID-19 vaccine products for different doses (heterologous schedule), and considers a total of 2 doses of any combination of EUL COVID-19 vaccines (e.g. 1 dose of BBV152 vaccine, and 1 dose of another EUL COVID-19 vaccine) to be a complete primary series.

Heterologous vaccination should only be implemented with careful consideration of current vaccine supply, vaccine supply projections, and other access considerations, alongside the potential benefits and risks of the specific products being used.

Vaccination schedule for immunocompromised persons [WHO, 2022 ]
WHO recommends and extended primary series including an additional (third) dose for immunocompromised persons aged 18 years and older, administered 1–3 months after the second dose in the standard primary series.
A booster (fourth) dose administered 3–6 months after the additional (third) dose should be considered for immunocompromised persons.

Indications and contraindications

Indications

The Bharat Biotech COVID-19 vaccine is indicated in individuals 18 of age and over [WHO, 2022 ].

Contrandications

The vaccine is contraindicated in individuals with a known history of a severe allergic reaction to any component of the Bharat Biotech COVID-19 vaccine [WHO, 2022 ]. (See the list of ingredients under 'General characteristics' in the extended version).

The second dose of the vaccine should NOT BE GIVEN to those who have experienced anaphylaxis to the first dose of Bharat Biotech COVID-19 vaccine.

Close observation for at least 30 minutes is recommended following vaccination.

Precautions

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Allergic reactions [WHO, 2022 ].
Persons with a history of anaphylaxis to any other vaccine or injectable therapy should be observed for 30 minutes after vaccination in health care settings where anaphylaxis can be immediately treated.

Pregnancy [WHO, 2022 ].
Available data from clinical trials are still insufficient to assess vaccine safety or efficacy of the Bharat Biotech COVID-19 vaccine in pregnancy. Emerging post-introduction pharmacovigilance data have not identified any pregnancy-related safety concerns.

WHO recommends the use of the Bharat Biotech COVID-19 vaccine in pregnant women when the benefits of vaccination to the pregnant woman outweigh the potential risks. To help pregnant women make this assessment, they should be provided with information about the risks of COVID-19 in pregnancy, the likely benefits of vaccination, and the current limitations of safety data.
WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination.

Breastfeeding [WHO, 2022 ].
WHO recommends using the Bharat Biotech COVID-19 vaccine in breastfeeding as in non-breastfeeding women. This is based on the following considerations: (a) Vaccine effectiveness is expected to be similar in breastfeeding women as in other adults, and (b) Bharat Biotech COVID-19 is not a live virus vaccine, and it is biologically and clinically unlikely to pose a risk to the breastfeeding child.
WHO does not recommend discontinuing breastfeeding after vaccination.

Children and adolescents [WHO, 2022 ].
Until EUL authorization for this age group has been granted, vaccination of individuals below 18 years of age with this vaccine is not recommended.

Older persons [WHO, 2022 ].
Vaccination is recommended for older persons, booster dose is recommended for the highest and high priority-use groups such as older adults, administered 4–6 months after completion of the primary series.

Persons living with HIV [WHO, 2022 ].

Given that the vaccine is nonreplicating, persons living with HIV who are well controlled may be vaccinated with the standard primary series of two doses. Counseling should be provided to inform the individual benefit-risk assessment.

Persons with previous SARS-CoV-2 infection [WHO, 2022 ].
Vaccination may be offered regardless of a person’s history of symptomatic or asymptomatic SARS-CoV-2 infection.
The optimal time interval between a natural infection and vaccination is not yet known. An interval of 3 months could be considered.

Persons with current acute COVID-19 [WHO, 2022 ].

Persons with acute PCR-confirmed COVID-19 should not be vaccinated until after they have recovered from acute illness and the criteria for discontinuation of isolation have been met.

Persons who previously received passive antibody therapy for COVID-19[WHO, 2022 ]
Although some reduction in vaccine-induced antibody titers has been observed in this group, the balance of benefits versus risks favors vaccination.

Other precautions
Vaccination should be postponed in individuals with an acute febrile illness (body temperature over 38.5ºC) until they are afebrile [WHO, 2022 ].

Co-administration with other vaccines [WHO, 2022 ].
For adults, COVID-19 vaccines may be administered concomitantly or at any time before or after other adult vaccines, including: live attenuated vaccines, inactivated, adjuvanted, or non-adjuvanted vaccines.

Adults: Based on several co-administration studies of COVID-19 and other adult vaccines, vaccines for COVID-19 can be administered concomitantly with, or at any time before or after, other adult vaccines, including live attenuated vaccines, inactivated, vaccines with or without adjuvant [WHO, 2022 ].

When administered concomitantly, the vaccines should be injected at separate sites, preferably different extremities [WHO, 2022 ].

Storage and logistics

Storage

Bharat Biotech COVID-19 vaccine is provided as a suspension stored at 5°C/41°F (between 2°C to 8°C [35° to 46°F]).
Unopened vaccine vials can be stored refrigerated between 2°C to 8°C [35° to 46°F] for up to 9 months [WHO, 2021 ].
Protect the vials from light.
Do not freeze.

Administration logistics

Inspect the vial before administration.
The vial should be discarded if particles or differences are observed in the described appearance of the vaccine.
Gently invert the vaccine vial several times to homogenize the contents. Do not shake.

Storage after first puncture

Once the multidose vial of the vaccine is opened, it can be stored between 2°C and 8°C (36 ° F to 46 ° F) during the immunization session and discarded within 6 hours of opening (first puncture) or at the end of the session, whichever comes first [WHO, 2021 ].

The single-dose vial should be used immediately after opening.
Record the date and time the vial should be discarded.
To improve traceability, the name and batch number of the administered product should be clearly recorded.

Administration

1.Using aseptic technique, clean the vial stopper with a single-use antiseptic swab.
2. Use a 3 ml reuse prevention syringe (RUP) or a 5 ml RUP syringe, and a 21G or narrower needle.
3. Gently invert the vial to mix, and withdraw the 0.5 ml dose. If the amount of vaccine remaining in the vial cannot provide a full 0.5 ml dose, discard the vial and the remaining volume.
4. Administer the vaccine intramuscularly, preferably into the deltoid muscle. Do not administer the vaccine intravascularly, subcutaneously, or intradermally.

Disposal

Due to the high risk that discarded vials of COVID-19 vaccines may be recovered, it is essential that they are guaranteed to be safely disposed of at the site of use; or study the possibility of applying reverse logistics, if the safe treatment and disposal of vaccine residues cannot be guaranteed, so that they are transferred to the place established for that purpose. Otherwise, consider the possibility that the discarded vaccine vials are shredded, if there is a safe way to do so [WHO, 2021 ].

Clinical studies - general characteristics

The following randomized clinical trials have reported vaccine efficacy and/or safety data:

Phase 1/2:
The BBIL/BBV152-A/2020 trial, (NCT04471519 [Bharat Biotech International Limited, 2020 ]) was conducted in India and initiated in July 2020. Phase 1 enrolled healthy adults aged 18 to 55 years who were randomly assigned to receive one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or a control vaccine group. Two intramuscular doses were administered on days 0 and 14. Phase 2 included adults and adolescents (12 to 65 years) who were randomly assigned (1:1) to receive 3 μg with Algel-IMDG or 6 μg with Algel-IMDG. IMDG [Venkata V Edara, 2022 ], [Deshpande GR, 2022 ], [Vadrevu KM, 2022 ], [Ella R, 2021 ], [Ella R, 2021 ], [Bharat Biotech International Limited, 2020 ], [Krishna Mohan Vadrevu, 2022 ].

Phase 3:
The trial conducted by Ella R et al. (NCT04641481 [Bharat Biotech International Limited, 2020 ]) in India from November 2020, enrolled 24,419 adults aged 18 years and older randomized in a 1:1 ratio, who received either two 6 µg intramuscular doses of BBV152 or placebo on days 0 and 28 [Ella R, 2021 ].

Phase 4:
The MnM study (CTRI/2021/08/035648 [Christian Medical College, 2021 ]) was conducted in India since August 2021. Participants who received two doses each of Covishield (ChAdOx1 nCoV-19, n=200) or Covaxin (BBV152, n=205) were randomized to receive either Covishield or Covaxin as a booster dose in a 1:1 ratio [Winsley Rose, 2022 ][Rose W, 2023 ].

Vaccine efficacy and effectiveness

Efficacy of preclinical studies on the vaccine

Immunogenicity of the vaccine has been evaluated in mice, rats and rabbits [Ganneru B, 2021 ], Syrian hamsters [Mohandas S, 2021 ] and non-human primates [Yadav PD, 2021 ].

Ganneru et al. assessed immunogenicity of the vaccine at two antigen concentrations (3μg and 6μg), with two different adjuvants, in mice, rats and rabbits. All formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations, in all three species. The formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-γ+ CD4+ T lymphocyte response [Ganneru B, 2021 ].

Mohandas et al. assessed immunogenicity of different vaccination regimes in Syrian hamsters (BBV152A, BBV152B, and BBV152C). All the regimes induced significant titers of SARS-CoV-2-specific IgG and neutralizing antibodies. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. Of the three candidates, BBV152A showed the better response.

Yadav et al. assessed immunogenicity of three different vaccine schedules, at day 0 and 14, in 20 rhesus macaques. A protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd week post-immunization. No evidence of pneumonia was observed by histopathological examination in the vaccinated groups [Yadav PD, 2021 ].

Efficacy of the vaccine in clinical trials

Main immunogenicity outcomes

BBIL/BBV152-A/2020 trial evaluated the immunogenicity of a two-dose schedule with three different formulations of the vaccine in participants 12 to 65 years old. The vaccine induced high neutralising antibody responses that remained at 3 months after the second vaccination. The 6 µg with Algel-IMDG formulation was selected for the phase 3 efficacy trial [Ella R, 2021 ].

The phase 3 BBIL/BBV152-C/2020 trial evaluated the consistency of immune responses from three consecutive manufacturing batches. The results showed that the neutralizing antibodies of the mean antibody titers in the groups that received lots 1, 2, 3 or placebo were 130.3 (95% CI: 105.8-160.4), 121.2 (97.6-150.5), 125.4 (101.3-155.1), and 13.7 (10.7-17.4) respectively on day 56. Antibody titers were higher (194, 3 [95% CI 134.4-280.9, n = 48] in vaccinated participants who were seropositive for SARS-CoV-2 at baseline [40b42c59d7d5e26930510ba5afíritu78a6a82e36f].

Main efficacy outcomes of the Bharat Biotech COVID-19 vaccine

Key messages

Bharat Biotech COVID-19 vaccine reduces the risk of contracting COVID-19

Bharat Biotech COVID-19 vaccine reduces the risk of contracting severe COVID-19

Contracting COVID-19 (measured at least 14 days after the second injection)

The relative risk of contracting COVID-19 in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 0.23 (95% CI 0.15 to 0.35). This means Bharat Biotech COVID-19 vaccine reduced the risk of contracting COVID-19 by 77%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19. Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 106 people not receiving Bharat Biotech COVID-19 vaccine out of 8502 presented this outcome (12 per 1000) versus 24 out of 8471 in the group that did receive it (3 per 1000). In other words,10 less to 8 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 77%, or that the intervention reduced the risk of contracting COVID-19 by 77 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 111. Which means that 111 people need to receive the vaccine for one of them to not contracting COVID-19.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as moderate. We downgraded the certainty of the evidence due to the risk of bias in the included studies.

Contracting severe COVID-19 (measured at least 14 days after the second injection)

The relative risk of contracting severe COVID-19 in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 0.07 (95% CI 0.01 to 0.51). This means Bharat Biotech COVID-19 vaccine reduced the risk of contracting severe COVID-19 by 93%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting severe COVID-19. Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 15 people not receiving Bharat Biotech COVID-19 vaccine out of 8502 presented this outcome (2 per 1000) versus 1 out of 8471 in the group that did receive it (0 per 1000). In other words,2 less to 1 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 93%, or that the intervention reduced the risk of contracting severe COVID-19 by 93 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 500. Which means that 500 people need to receive the vaccine for one of them to not contracting severe COVID-19.

Efficacy of the vaccine in subgroups

Contracting COVID-19 (>60y) (measured at least 14 days after the second injection)

The relative risk of contracting COVID-19 (>60y) in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 0.34 (95% CI 0.12 to 0.92). This means Bharat Biotech COVID-19 vaccine reduced the risk of contracting COVID-19 (>60y) by 66%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19 (>60y). Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 16 people not receiving Bharat Biotech COVID-19 vaccine out of 965 presented this outcome (17 per 1000) versus 5 out of 893 in the group that did receive it (6 per 1000). In other words,15 less to 1 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 66%, or that the intervention reduced the risk of contracting COVID-19 (>60y) by 66 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 91. Which means that 91 people need to receive the vaccine for one of them to not contracting COVID-19 (>60y).

Summary of findings (iSoF)

Efficacy and effectiveness of the vaccine in subgroups

Sex
Randomized trials
The differential efficacy of the vaccine in sex groups was not reported in the phase 3 trial conducted by Ella et al. [Ella R, 2021 ].

Age
Randomized trials
The proportion of patients >60 years of age in the phase 3 trial conducted by Ella et al. was 10.95% (1858 out of 16973 participants) [Ella R, 2021 ].
Vaccine efficacy was 67.8% (95% CI, 8% to 90%) in the ≥60 years group [Ella R, 2021 ].

In the phase 1/2 trial BBIL/BBV152-A/2020, the percentage of participants by age was: 12-17 years: 3.7%; 18-54 years: 92%; 55-65: 4.3%. Seroconversion rates across the three age groups were similar [Ella R, 2021 ].

Children and adolescents
Randomized trials
Children and adolescents were excluded from the phase 3 trial conducted by Ella et al. [Ella R, 2021 ], therefore no data are available for this subgroup.

In the phase 1/2 trial BBIL/BBV152-A/2020, the percentage of participants 12 to 17 years of age was 3.7% (14 out of 380). Seroconversion rate in this age group was similar. Children <12 years were excluded [Ella R, 2021 ].

Pregnancy
Randomized trials
Pregnant women were excluded from the phase 3 trial conducted by Ella et al. [Ella R, 2021 ], therefore no data are available for this subgroup.

In the phase 1/2 trial BBIL/BBV152-A/2020, pregnant females were excluded, so no data are available for this subgroup [Ella R, 2021 ].

Breast-feeding
Randomized trials
Breastfeeding women were excluded from the phase 3 trial conducted by Ella et al. [Ella R, 2021 ], therefore no data are available for this subgroup.

In the phase 1/2 trial BBIL/BBV152-A/2020, breastfeeding females were excluded, so no data are available for this subgroup [Ella R, 2021 ].

Immunocompromised persons
Randomized trials
Immunocompromised persons were excluded from the phase 3 trial conducted by Ella et al. [Ella R, 2021 ], therefore no data are available for this subgroup.

In the phase 1/2 trial BBIL/BBV152-A/2020, immunocompromised patients were excluded, so no data are available for this subgroup [Ella R, 2021 ].

Vaccine effectiveness (other comparative studies)

Contracting COVID-19
Sumit Malhotra et al. was a cohort study conducted in India. The study enrolled 12,237 participants: 8,248 vaccine group; 3,989 control group. Based on data from different HCWs employed at the All India Institute of Medical Sciences (AIIMS), New Delhi, India, a public-funded, teaching and multi-speciality tertiary care institute, between April 10 and June 24, 2021, the study results showed a vaccine effectiveness of 44% (95% CI 37 to 51) against symptomatic infection, hospitalization or death and a vaccine effectiveness of 61% (95% CI 37 to 76) against hospitalization or death [Sumit Malhotra, 2022 ].

Malhotra S et al. was a retrospective cohort study conducted in India. The study included 1,917 health care workers for vaccine effectiveness assessment: 1,089 in fully vaccinated group, 356 in partially vaccinated group and 472 in unvaccinated group. The aim was to assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI 77% to 92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection [Malhotra S, 2022 ].

Bhattacharya D was a case control study conducted in India that included 1,614 participants: 864 cases and 750 controls. The aim was to assess the effectiveness of two doses of vaccines against COVID-19 infection. Adjusted vaccine effectiveness after second dose of Covaxin was 74% (95% CI, 50.5% to 86.0%) [Bhattacharya D, 2022 ].

Contracting severe COVID-19
Sumit Malhotra et al. was a cohort study conducted in India. The study enrolled 12,237 participants: 8,248 vaccine group; 3,989 control group. Based on data from different HCWs employed at the AllIndia Institute of Medical Sciences (AIIMS), New Delhi, India, a public-funded, teaching and multi-speciality tertiary care institute, between April 10 and June 24, 2021, the study results showed a vaccine effectiveness of 44% (95% CI 37 to 51) against symptomatic infection, hospitalization or death and a vaccine effectiveness of 61% (95% CI 37 to 76) against hospitalization or death. [Sumit Malhotra, 2022 ].

Bhatnagar T was a case-control study conducted in India. The study enrolled 3684 participants older than 45 years that were attended 11 hospitals between May and July 2021. For the primary vaccine effectiveness (VE) analysis, the proportion of fully vaccinated and unvaccinated individuals was compared among cases (test-confirmed severe COVID-19 patients, n= 1143) and controls (negative RT-PCR for SARS-CoV-2, n= 2541). The study results showed that VE in fully vaccinated individuals was 71% (95% CI 57 to 81%) against severe COVID-19 and that it was significantly higher (P = 0.027) than partial vaccination [39% (95% CI: 2-62%)]. The VE for fully vaccinated individuals with an interval of 6-8 weeks for BBV152/Covaxin was 93% (95% CI: 34-99%). [Bhatnagar T, 2022 ]

Heidarzadeh et al was a test negative case-control study to estimate the effectivenesss of COVID-19 vaccines against hospitalization and death in Guilan Province of Iran, from May to December 2021. This study included population aged 5 years and above by extracting information from local databases (MCMC and SIB). The total study population was 42,084 including 19,500 cases and 22,586 controls. For the Covaxin + Covaxin schedule, the Vaccine Effectiveness (VE) against hospitalization (regular admission) was 41% (95% CI, -6.08 to 96%) within 1-30 days and 96% (95% CI, 68% to 99.5%) ≥ 151 days after the second dose. VE against death was 4% (95% CI, -6.71 to 79%) within 91-120 days after the second dose. [Heidarzadeh A, 2022 ]

Transmission
No studies reported or assessed this outcome

Efficacy and effectiveness against SARS-CoV-2 variants

Immunogenicity outcomes
Alpha (B.1.1.7)
Sapkal GN et al was a non-comparative study (neutralizing capacity from recipients' sera) in India, in which 38 vaccine recipients were included. The study reported data from 4 weeks post immunization. The results showed that Bharat Biotech vaccine-induced antibodies show no significant decrease in neutralisation activity against the Alpha (B.1.1.7) variant. Median ratio of 50% neutralisation of sera was 0.8 compared with hCoV-19/India/2020770 against mutant hCoV-19/India/20203522 (B.1.1.7 variant) Non-parametric test for the comparison of the PRNT50 values from different groups revealed non-significant difference [Sapkal GN, 2021 ].

BBIL/BBV152-A/2020 was a phase 2, randomized, controlled, trial in India, in which 184 vaccine recipients were included. The study reported data from 243 days post-immunization. The results showed that 6 months after a two-dose Bharat Biotech vaccination series cell-mediated immunity and neutralizing antibodies to both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, and Delta plus) persisted above baseline, although the magnitude of the responses had declined. Neutralizing antibodies against homologous and heterologous SARS-CoV-2 variants increased 19- to 97-fold after a third vaccination[Krishna Mohan Vadrevu, 2022 ].

Vikkurthi et al. examined the immune memory in 97 SARS-CoV-2 unexposed individuals who had received BBV152 vaccine, up to 6 months (median, 4 months) after 2-dose vaccination. They compared the vaccine-induced responses with the immune memory in 99 individuals recovered from mild COVID-19. The samples in the infection group were collected between October 2020 and January 2021. The samples were collected 130 or 214 days (median) post the second dose of BBV152 vaccine or the diagnosis of COVID-19, respectively. The neutralizing potential: vaccine-induced antibodies had no significant impact on the Alpha variant (1.2-fold vs ancestral). Breadth of RBD-specific B cells in their reactivity to the SARS-CoV-2 variants: The modest reduction of 1.5 to 2-fold was observed against the Alpha variant over the ancestral virus RBD-specific IgG+ B cells. BBV152-induced CD4+ T cells: were not reduced significantly against Alpha as compared with the ancestral virus spike protein (mean %, ancestral: 0.39±0.07; Alpha: 0.31±0.05). The reactivity profile of CD4+ T cells acquired from natural infection was comparable with that of the vaccine, except that the median decline was ~2-fold for Alpha (P=0.004) [Vikkurthi R, 2022 ].

Beta (B.1.351)
Yadav PD et al. conducted a non-comparative study (neutralizing capacity from recipients' sera) in India, in which they included 17 vaccine recipients. The study reported data from 28 days post immunization. The results showed that the Bharat Biotech vaccine had shown a significant reduction in neutralization titer for Beta variant (GMT: 187.5 (95%CI 129.3 to 271.9)) [Yadav PD, 2021 ].

Deshpande et al. was a comparative study conducted in India, derived from the BBIL/BBV152-A/2020 trial. The study evaluated the antibody responses in sera of participants who received two doses of Covaxin collected 6 months post second dose (2 dose group, n = 51) and 28 days after receiving a booster dose (booster dose group, n = 49) and its impact against the Beta VOC. The anti-SARS CoV-2 spike (S1-RBD) and nucleocapsid (N) IgG binding antibodies levels were characterized by ELISA and the plaque reduction neutralization test (PRNT) was used to assess the neutralizing antibody (Nab) capacity against prototype B.1, Alpha, Beta, Delta and Omicron variants. The study showed a fold increase of 2.8 (95% CI 2.65 to 2.95) in anti-S1-RBD IgG GM titers between the 2 dose and booster dose groups and a fold increase of 14.7 (95% CI 26.87 to 8.04), p=0.0002 in NAbs titers against Beta variant between the two groups [Deshpande GR, 2022 ].

Vikkurthi et al. examined the immune memory in 97 SARS-CoV-2 unexposed individuals who had received BBV152 vaccine, up to 6 months (median, 4 months) after 2-dose vaccination. They compared the vaccine-induced responses with the immune memory in 99 individuals recovered from mild COVID-19. The samples in the infection group were collected between October 2020 and January 2021. The samples were collected 130 or 214 days (median) post the second dose of BBV152 vaccine or the diagnosis of COVID-19, respectively. The neutralizing potential: vaccine-induced antibodies declined significantly against Beta (1.7-fold vs ancestral; P=0.03) variant. Breadth of RBD-specific B cells in their reactivity to the SARS-CoV-2 variants: The modest reduction of 1.5 to 2-fold was observed against the Beta variant over the ancestral virus RBD-specific IgG+ B cells. BBV152-induced CD4+ T cells:. A significant decline was observed in the Beta variant, the median reduction was 1.3-fold over the ancestral virus (0.25±0.04; P=0.004). The reactivity profile of CD4+ T cells acquired from natural infection was comparable with that of the vaccine, except that the median decline was ~2-fold for Beta (P=0.0003) [Vikkurthi R, 2022 ].

Delta (B.1.617.2)
Pragya D Yadav et al. conducted a comparative study (neutralizing capacity from recipients' sera) in India, which included 42 recipients of the Bharat Biotech COVID-19 vaccine. The study reported data from 16 weeks post immunization (median). The results showed a minor reduction was observed in the neutralizing antibody titer in COVID- 19 recovered cases full Bharat Biotech vaccinated (reduction: 1.3-fold) [Pragya D Yadav, 2021 ].

Yadav PD et al. conducted a non-comparative study (neutralizing capacity from recipients' sera) in India, in which they included 17 vaccine recipients. The study reported data from 28 days post immunization. The results showed that the vaccinees had shown a significant reduction in neutralization titer for Deta variant (GMT 61.57 (95% CI 36.3 to104.3)) [Yadav PD, 2021 ].

Das et al. was a non-comparative study conducted in India, the study analyzed the immune response against wild variants, Delta and Omicron after a first dose of the Bharat vaccine. The study updated data from 94 people scheduled to receive their first dose of the Bharat vaccine for COVID-19. The results are based on blood samples collected one day before and 4 weeks after the first dose of the vaccine. The study showed increases in neutralizing test titers for all variants compared to baseline. However, this increase was insignificant or modest against the delta and omicron variants in people who had been infected before receiving the vaccine [Das, S., 2022 ].

Deshpande et al. was a comparative study conducted in India, derived from the BBIL/BBV152-A/2020 trial. The study evaluated the antibody responses in sera of participants who received two doses of Covaxin collected 6 months post second dose (2 dose group, n = 51) and 28 days after receiving a booster dose (booster dose group, n = 49) and its impact against the Delta VOC. The anti-SARS CoV-2 spike (S1-RBD) and nucleocapsid (N) IgG binding antibodies levels were characterized by ELISA and the plaque reduction neutralization test (PRNT) was used to assess the neutralizing antibody (Nab) capacity against prototype B.1, Alpha, Beta, Delta and Omicron variants. The study showed a fold increase of 2.8 (95% CI 2.65 to 2.95) in anti-S1-RBD IgG GM titers between the 2 dose and booster dose groups and a fold increase of 16.54 (95% CI 34.08 to 8.03), p<0.0001 in NAbs titers against Delta variant between the two groups [Deshpande GR, 2022 ].

Vadrevu et al. conducted a report on the immunogenicity of the Covaxin booster dose against the ancestral variant and those of concern, at one year of follow-up of the BBIL/BBV152-A/2020 trial. Patients were followed up to 6 months after the second dose to assess the durability of immune responses, then participants who previously received the 6 µg dose with Algel-IMDG were randomized to receive a third (boost) dose of BBV152 or placebo. Neutralizing antibody GMTs against SARS-CoV-2 variants were assessed by PRNT on days 208 and 243 in the booster group. The GMTs against the Delta and Delta Plus variant were 369 (222–614) and 310 (198–483), 410- and 281-fold increases from day 208, respectively. Sera collected after 6 months after the third dose were evaluated for neutralization efficacy against Delta by PRNT50, obtaining GMT 159.9 (55.8–240.8) and a seroconversion rate of 96.8 ( 81.5–99.8) in the booster group. [Vadrevu KM, 2022 ]

Vikkurthi et al. examined the immune memory in 97 SARS-CoV-2 unexposed individuals who had received BBV152 vaccine, up to 6 months (median, 4 months) after 2-dose vaccination. They compared the vaccine-induced responses with the immune memory in 99 individuals recovered from mild COVID-19. The samples in the infection group were collected between October 2020 and January 2021. The samples were collected 130 or 214 days (median) post the second dose of BBV152 vaccine or the diagnosis of COVID-19, respectively. The neutralizing potential: vaccine-induced antibodies declined significantly against the Delta (2-fold vs ancestral; P<0.0001). Breadth of RBD-specific B cells in their reactivity to the SARS-CoV-2 variants: A ~2-fold reduction in vaccine-induced IgG+ B cells was observed against the Delta variant. BBV152-induced CD4+ T cells: were not reduced significantly against Delta as compared with the ancestral virus spike protein (mean %, ancestral: 0.39±0.07; Delta: 0.28±0.05) [Vikkurthi R, 2022 ].

Omicron (B.1.1.529)
BBIL/BBV152-A/2020 was a phase 2, randomized, controlled, trial in India, in which 184 vaccine recipients were included. The study reported data from 243 days post-immunization. The results showed that 6 months after a two-dose Bharat Biotech vaccination series cell-mediated immunity and neutralizing antibodies to both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, and Delta plus) persisted above baseline, although the magnitude of the responses had declined. Neutralizing antibodies against homologous and heterologous SARS-CoV-2 variants increased 19- to 97-fold after a third vaccination[Krishna Mohan Vadrevu, 2022 ].

Deshpande et al. was a comparative study conducted in India, derived from the BBIL/BBV152-A/2020 trial. The study evaluated the antibody responses in sera of participants who received two doses of Covaxin collected 6 months post second dose (2 dose group, n = 51) and 28 days after receiving a booster dose (booster dose group, n = 49) and its impact against the Omicron VOC. The anti-SARS CoV-2 spike (S1-RBD) and nucleocapsid (N) IgG binding antibodies levels were characterized by ELISA and the plaque reduction neutralization test (PRNT) was used to assess the neutralizing antibody (Nab) capacity against prototype B.1, Alpha, Beta, Delta and Omicron variants. The study showed a fold increase of 2.8 (95% CI 2.65 to 2.95) in anti-S1-RBD IgG GM titers between the 2 dose and booster dose groups and a fold increase of 18.53 (95% CI 28.92 to 11.88), p=0.0002 in NAbs titers between the two groups [Deshpande GR, 2022 ].

Vadrevu et al. conducted a report on the immunogenicity of the Covaxin booster dose against the ancestral variant and those of concern, at one year of follow-up of the BBIL/BBV152-A/2020 trial. Patients were followed up to 6 months after the second dose to assess the durability of immune responses, then participants who previously received the 6 µg dose with Algel-IMDG were randomized to receive a third (boost) dose of BBV152 or placebo. The results showed an 18.5-fold increase in neutralizing antibody titers against the Omicron variant after the booster dose of BBV15215, compared to recipients who did not receive a boost. 90% of subjects receiving the third dose of COVAXIN® showed neutralizing activity against the Omicron variant when tested 28 days after the third dose of serum. Sera collected 6 months after the third dose were evaluated for neutralization efficacy against Omicron by PRNT50, yielding GMT 25.7 (13.0–50.6) and a seroconversion rate of 93.5 ( 77.2–98.9) in the booster group. [Vadrevu KM, 2022 ]

Efficacy outcomes
Delta (B.1.617.2)
Ella R et al. was a multicenter, phase 3, randomized clinical trial conducted in 25 hospitals in India, where 16,973 participants were recruited (8,471 vaccine group and 8,502 placebo group). The study seeks to evaluate the efficacy of Bharat's biotech vaccine in preventing the first occurrence of symptomatic COVID-19 (any severity) starting at least 14 days after the second dose. The results showed an efficacy against symptomatic infection of 65.2% (95% CI 33.1 to 83.0) [Ella R, 2021 ].

Effectiveness outcomes
Delta (B.1.617.2)
Bhatnagar T was a case-control study conducted in India. The study enrolled 3684 participants older than 45 years that were attended 11 hospitals between May and July 2021. For the primary vaccine effectiveness (VE) analysis, the proportion of fully vaccinated and unvaccinated individuals was compared among cases (test-confirmed severe COVID-19 patients, n= 1143) and controls (negative RT-PCR for Sars-CoV-2, n= 2541). The study results showed that VE against the Delta variant and sub-lineages was 66% (95% CI: 42-80%) for complete dose and 41% (95% CI: 0-70%) for vaccination with a partial dose of BBV152/Covaxin (p= 0.261) [Bhatnagar T, 2022 ].

Vaccine efficacy and effectiveness for booster dose

Immunogenicity outcomes
BBIL/BBV152-A/2020 was a phase 2, randomized, controlled, trial in India, in which 184 vaccine recipients were included. The study reported data from 243 days post-immunization. The results showed that 6 months after a two-dose Bharat Biotech vaccination series cell-mediated immunity and neutralizing antibodies to both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, and Delta plus) persisted above baseline, although the magnitude of the responses had declined. Neutralizing antibodies against homologous and heterologous SARS-CoV-2 variants increased 19- to 97-fold after a third vaccination [Krishna Mohan Vadrevu, 2022 ].

A new BBIL/BBV152-A/2020 study report included 13 booster vaccine recipients. Data were collected 28 days after the booster dose. The study showed that All subjects showed neutralizing activity against the Delta variant. There was however a 1.5 fold reduction compared to neutralization against the vaccine strain. In addition, 90% of subjects showed neutralizing activity against the Omicron variant. There was however a 9.4 fold reduction compared to neutralization against the vaccine strain [Venkata V Edara, 2022 ].

Deshpande et al. was a comparative study conducted in India, derived from the BBIL/BBV152-A/2020 trial. The study evaluated the antibody responses in sera of participants who received two doses of Covaxin collected 6 months post second dose (2 dose group, n = 51) and 28 days after receiving a booster dose (booster dose group, n = 49) and its impact against the Omicron VOC. The anti-SARS CoV-2 spike (S1-RBD) and nucleocapsid (N) IgG binding antibodies levels were characterized by ELISA and the plaque reduction neutralization test (PRNT) was used to assess the neutralizing antibody (Nab) capacity against prototype B.1, Alpha, Beta, Delta and Omicron variants. The study showed a fold increase of 2.8 (95% CI2.65 to 2.95) in anti-S1-RBD IgG GM titers between the 2 dose and booster dose groups and a fold increase of 18.53 (95% CI 28.92 to 11.88), p=0.0002 in NAbs titers between the two groups [Deshpande GR, 2022 ].

Vadrevu et al. conducted a report on the immunogenicity of the Covaxin booster dose against the ancestral variant and those of concern, at one year of follow-up of the BBIL/BBV152-A/2020 trial. Patients were followed up to 6 months after the second dose to assess the durability of immune responses, then participants who previously received the 6 µg dose with Algel-IMDG were randomized to receive a third (boost) dose of BBV152 or placebo. The results showed persistence of cell-mediated and humoral immunity up to 12 months after vaccination, despite the decrease in the magnitude of antibody titers. Administration of a third dose of BBV152 increased neutralization titers against both homologous (D614G) and heterologous (Alpha, Beta, Delta, Delta Plus, and Omicron) strains with a slight increase in B-cell memory responses. Thus, the seronversion rate remains high in boosted compared with unboosted recipients, even after 6 months, after the third dose against the variants. No serious adverse events except injection site pain, itching, and redness were observed. [Vadrevu KM, 2022 ]

The MnM study was a phase 4 randomized trial conducted in India including 404 participants, 200 received an AstraZeneca primary schedule and 204 received a Covaxin primary schedule. The participants were randomized to receive an AstraZeneca or Covaxin booster dose. The study assessed the immunogenicity 28 days after the booster dose. The Geometric mean concentration of anti-SARS-CoV-2 Spike IgG was 48,473.94 (95% CI, 38,529.56-60,984.95) with a geometric mean fold ratio of 5.32 (95% CI, 3.55-7.99) [Rose W, 2023 ].

Vaccine efficacy and effectiveness for heterologous schedule

Currently, there are no studies that have assessed the vaccine immunogenicity outcomes on heterologous regimen.

Vaccine efficacy and effectiveness for heterologous booster schedule

The MnM study was a phase 4 randomized trial conducted in India including 404 participants, 200 received an AstraZeneca primary schedule and 204 received a Covaxin primary schedule. The participants were randomized to receive an AstraZeneca or Covaxin booster dose. The study assessed the immunogenicity 28 days after the booster dose. The geometric mean concentration (GMC) of anti-SARS-CoV-2 Spike IgG was 36,190.78 (95% CI, 30,526.64-42,905.88) with a geometric mean fold ratio (GMFR) of 2.81 (95% CI, 2.21-3.57) in the AstraZeneca+Covaxin group, and the GMC was 241,681.6 (95% CI, 201,380.2-290,048.3) with a GMFR of 31.19 (95% CI, 20.38-47.74) in the Covaxin+AstraZeneca group [Rose W, 2023 ].

Safety of the vaccine

Safety of the vaccine in preclinical studies

The safety of the vaccine has been evaluated in mice, rats and rabbits [Ganneru B, 2021 ]. Other preclinical studies did not assess safety outcomes [Mohandas S, 2021 ],[Yadav PD, 2021 ].

Ganneru et al assessed preclinical safety of either adjuvant-alone (Algel-IMDG) or three formulations of the vaccine in mice, rats and rabbits. The studies did not indicate any undesirable pathological changes and systemic toxicity, except local reactogenicity at the site of injection. Mutagenicity assay performed with Algel-IMDG at various concentrations revealed the adjuvant-alone or in combination with the adjuvanted vaccine formulation was non-mutagenic [Ganneru B, 2021 ].

Safety of the vaccine in clinical trials

Local adverse events after the 1st dose (measured at least 7 days after vaccination)

The relative risk of local adverse events after the 1st dose in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 1.08 (95% CI 0.94 to 1.23). This means Bharat Biotech COVID-19 vaccine increased the risk of local adverse events after the 1st dose by 8%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: local adverse events after the 1st dose. Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 399 people not receiving Bharat Biotech COVID-19 vaccine out of 12874 presented this outcome (31 per 1000) versus 431 out of 12879 in the group that did receive it (33 per 1000). In other words,2 less to 7 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 8%, or that the intervention increased the risk of local adverse events after the 1st dose by 8 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNH is 500. Which means that 500 people need to receive the vaccine for one of them to present local adverse events after the 1st dose.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Local adverse events after the 2nd dose (measured at least 7 days after vaccination)

The relative risk of local adverse events after the 2nd dose in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 1.07 (95% CI 0.9 to 1.26). This means Bharat Biotech COVID-19 vaccine increased the risk of local adverse events after the 2nd dose by 7%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: local adverse events after the 2nd dose. Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 260 people not receiving Bharat Biotech COVID-19 vaccine out of 12874 presented this outcome (20 per 1000) versus 278 out of 12879 in the group that did receive it (21 per 1000). In other words, people per did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 7%, or that the intervention increased the risk of local adverse events after the 2nd dose by 7 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNH is 1000. Which means that 1000 people need to receive the vaccine for one of them to present local adverse events after the 2nd dose.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Systemic adverse events after the 1st dose (measured at least 7 days after vaccination)

The relative risk of systemic adverse events after the 1st dose in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 1.34 (95% CI 1.14 to 1.58). This means Bharat Biotech COVID-19 vaccine increased the risk of systemic adverse events after the 1st dose by 34%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: systemic adverse events after the 1st dose. Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 247 people not receiving Bharat Biotech COVID-19 vaccine out of 12874 presented this outcome (19 per 1000) versus 331 out of 12879 in the group that did receive it (25 per 1000). In other words,3 more to 11 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 34%, or that the intervention increased the risk of systemic adverse events after the 1st dose by 34 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNH is 167. Which means that 167 people need to receive the vaccine for one of them to present systemic adverse events after the 1st dose.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Systemic adverse events after the 2nd dose (measured at least 7 days after vaccination)

The relative risk of systemic adverse events after the 2nd dose in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 1.13 (95% CI 0.93 to 1.36). This means Bharat Biotech COVID-19 vaccine increased the risk of systemic adverse events after the 2nd dose by 13%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: systemic adverse events after the 2nd dose. Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 205 people not receiving Bharat Biotech COVID-19 vaccine out of 12874 presented this outcome (16 per 1000) versus 231 out of 12879 in the group that did receive it (18 per 1000). In other words,1 less to 6 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 13%, or that the intervention increased the risk of systemic adverse events after the 2nd dose by 13 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNH is 500. Which means that 500 people need to receive the vaccine for one of them to present systemic adverse events after the 2nd dose.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Any adverse event (median follow up 146 days)

The relative risk of any adverse event in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 1 (95% CI 0.94 to 1.07). This means Bharat Biotech COVID-19 vaccine increased the risk of any adverse event by 0%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: any adverse event . Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 1597 people not receiving Bharat Biotech COVID-19 vaccine out of 12874 presented this outcome (124 per 1000) versus 1597 out of 12879 in the group that did receive it (124 per 1000). In other words,8 less to 8 more people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk increase of 0%, or that the intervention increased the risk of any adverse event by 0 percentage points.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Serious adverse events (median follow up 146 days)

The relative risk of serious adverse events in the group that received Bharat Biotech COVID-19 vaccine, versus the group that received control vaccine was 0.65 (95% CI 0.43 to 0.97). This means Bharat Biotech COVID-19 vaccine reduced the risk of serious adverse events by 35%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: serious adverse events. Comparison: control vaccine versus Bharat Biotech COVID-19 vaccine

In the trials identified in this review, 60 people not receiving Bharat Biotech COVID-19 vaccine out of 12874 presented this outcome (5 per 1000) versus 39 out of 12879 in the group that did receive it (3 per 1000). In other words,3 less to 0 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 35%, or that the intervention reduced the risk of serious adverse events by 35 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 500. Which means that 500 people need to receive the vaccine for one of them to not contract serious adverse events.

Applying the GRADE approach [The GRADE Working Group, 2013 ], we assessed the certainty of the evidence for this outcome as high.

Summary of findings (iSoF)

Safety of the vaccine in subgroups

Sex
Randomized trials
There are no phase 3 randomized trials that have yet reported outcome data.

The differential safety of the vaccine in sex groups was not reported in the phase 1/2 trial BBIL/BBV152-A/2020 [Ella R, 2021 ].

Age
Randomized trials
In the phase 3 randomized trial conducted by Ella et al. the proportion of participants 60 years of age or older was 10.7% (2761 out of 25753) in the safety population. The proportion of participants >60 years that experienced adverse events was not reported in detail. However, no specific safety concerns were identified in this subgroup [Ella R, 2021 ].

Adults older than 65 years were not included in the phase 1/2 trial. Safety in the different age groups included was not reported [Ella R, 2021 ].

Children and adolescents
Randomized trials
Children and adolescents below 18 years of age were excluded from the phase 3 trial conducted by Ella et al., therefore no data are available for this subgroup [Ella R, 2021 ].

In the phase 1/2 trial BBIL/BBV152-A/2020, the percentage of participants 12 to 17 years of age was 3.7% (14 out of 380). Differential safety in this age group was not reported. Children <12 years were excluded [Ella R, 2021 ].

Pregnancy
Randomized trials
Pregnant women were excluded from the phase 3 trial conducted by Ella et al. therefore no data are available for this subgroup [Ella R, 2021 ].

In the phase 1/2 trial BBIL/BBV152-A/2020, pregnant females were excluded, so no data are available for this subgroup [Ella R, 2021 ].

Breast-feeding
Randomized trials
Breastfeeding women were excluded from the phase 3 trial conducted by Ella et al. therefore no data are available for this subgroup [Ella R, 2021 ].

In the phase 1/2 trial BBIL/BBV152-A/2020, breast-feeding females were excluded, so no data are available for this subgroup [Ella R, 2021 ].

Immunocompromised persons
Randomized trials
Immunocompromised persons were excluded from the phase 3 trial conducted by Ella et al. therefore no data are available for this subgroup [Ella R, 2021 ].

In the phase 1/2 trial BBIL/BBV152-A/2020, immunocompromised patients were excluded, so no data are available for this subgroup [Ella R, 2021 ].

Safety of the vaccine post-authorization

Post-authorization studies
Comparative studies
Joshi PC et al was a cohort study conducted in India. The study enrolled 3,235 participants: 828 vaccine group; 2,407 control group and assessed CT-Severity Score in vaccinated and non-vaccinated subjects who were diagnosed with COVID-pneumonia or were COVID suspects, based on findings in high resolution CT scans. The study results showed a CT Severity score median difference amongst non-vaccinated cases, cases with history of 1 dose and fully vaccinated cases of 7.0, 5.0, and 3.0 respectively in the 18-44 years group; 9.0, 7.0, and 7.0 respectively in the 45-59 years group and 9.0, 8.0 and 6.0 respectively in the >60 years group [Joshi PC, 2021 ].

Vadrevu KM et al was a cohort study conducted in 6 hospitals in India. The study included 526 children between the ages of 2 and 18 who were enrolled in three groups, depending on their age: group 1 (12 to 18 years, n= 176); group 2 (6 to 12 years old, n= 175) and group 3 (2 to 6 years old, n= 175). The objective of the study was to evaluate the safety, reactogenicity and immunogenicity of vaccination with the adult formulation of BBV152 in children, on days 0 (first dose) and 28 (second dose). The results of the study showed that there were no serious adverse events, deaths or withdrawals due to an adverse event during the period, with the exception of one case of COVID-19 in group 1. Local reactions consisted mainly of mild pain at the site of injection (35% of any group after the first dose and less than 25% after the second dose). Mild to moderate fever was reported in 5% in Group 1, 10% in Group 2, and 13% in Group 3. No cases of severe fever were reported, and total fever rates were 4% or less after the second dose [Vadrevu KM, 2022 ].

Non-comparative studies
Cherian S et al. was a non-comparative study carried out in India that included 724 participants with and without rheumatic and musculoskeletal diseases, vaccinated with at least one dose of Covashield or Covaxin vaccine. 436 (60.22%) participants had at least one adverse effect (AE). Four patients reported an arthritis flare that resolved within 5 days. No patient had severe AE or required hospitalization. All AE were self-limited. AE's do not differ between patients with autoimmune rheumatic disease (AIRD) or non-AIRD. Both the ChAdOx1 and BBV152 vaccines appear safe in patients with rheumatic and musculoskeletal diseases. [Cherian S, 2021 ]

Parida SP et al. was a non-comparative study conducted in India. The study enrolled 1826 participants and assessed the adverse events following COVID‐19 vaccine immunization at a tertiary care institution and also assessed the predictors of the adverse events following immunization. The study results showed that the major factors associated with AEFI were female sex, history of an allergicreaction, presence of comorbidities, acute infection in the past 3 months, and intake ofchronic medications. [Parida SP, 2022 ]

Nasergivehchi S et al. was a cohort study conducted in Iran. The study enrolled 334 healthcare workers who had contracted COVID-19 of different intensities and were vaccinated with different types of COVID-19 vaccine (Astrazeneca 12.9%, Sinopharm 16.2%, Sputnik 62.3%,Bharat Covaxin 6.9%) at least one month following recovery from the virus, between April 2021 and September 2021. The study assessed the incidence of headache following injection, showing that 39.2% of participants reported post-vaccination headache, with highest rates reported for AstraZeneca, followed by Sputnik V. [Nasergivehchi S, 2022 ]

Houshmand B et al. was a cross-sectional study conducted in Iran. The study included 1,205 respondents of a multicenter electronic questionnaire via an online platform over a 1-week period among vaccinated dental staff and dental students inquiring whether they experienced vaccine-related side-effects after vaccine administration. The majority of respondents received AstraZeneca (51.1%) and Sputnik (37.6%). The symptoms most frequently reported after vaccination were fatigue (79%), local pain in the injection site (77.4%), malaise (73%), and body pain (71.1%). Enrollees reported more onset of reactions on 0–12 h (44.1%) and 12–24 h (29.0%) after vaccine administration. [Houshmand B, 2022 ]

Jhar R et al was a retrospective cohort study conducted in India that reported adverse events following SARS-CoV-2 vaccination (AEFI), including data from 51,010 vaccine doses, between January and December, 2021. After Covaxin vaccination, 23 AEFI were reported, 2 of them were classified as serious events. The most common AEFI symptoms were generalized symptoms and pain.
[Jhaj R, 2022 ]

Monitoring

WHO indicates that after a vaccine is approved for use, regulators conduct robust monitoring of efficacy, as well as monitoring of safety and risk minimization (pharmacovigilance) activities. They need to continually monitor the safety of the vaccine to ensure that the benefits of the vaccine continue to outweigh the risks. [WHO, 2022 ]

Regarding safety surveillance and monitoring, serious adverse events, anaphylaxis and other severe allergic reactions, Bell's palsy, cases of multisystem inflammatory syndrome, cases of COVID-19 after vaccination resulting in hospitalization or death should be identified and recorded.

Regarding the effectiveness of the vaccine, the following should be monitored:
− Efficacy of the vaccine over time and whether protection can be prolonged with booster doses.
− Studies to investigate whether this vaccine reduces the transmission and viral spread of SARS-CoV-2.
− Evaluation and notification of vaccine failures and information on viral sequences.

Regarding the subgroups of interest
− Prospective studies on the safety of the COVID-19 vaccine in pregnant and lactating females.
− Occasional controlled trials on the safety and security of vaccination in children under 18 years of age.
− Safety data from vaccination in immunosuppressed people, including patients living with HIV and autoimmune diseases.

To review more information on the topic [WHO, 2022 ],[World Health Organization, 2021 ], [Organización Mundial de la Salud, 2022 ]

References

[WHO, 2021] WHO. WHO recommendation Bharat Biotech International Ltd – COVID-19 vaccine (Whole Virion Inactivated Corona Virus. 2021; WHO. WHO recommendation Bharat Biotech International Ltd – COVID-19 vaccine (Whole Virion Inactivated Corona Virus. 2021;
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COVID-19 vaccines	Country
Abdala of Center for Genetic Engineering and Biotechnology (CIGB)	Click to see the list
Ad5-nCoV-IH of CanSino Biologics New	Click to see the list
Aurora-CoV of Vector State Research Center of Virology and Biotechnology	Russia
Comirnaty (BNT162b2) of Pfizer-BioNTech	Click to see the list
Comirnaty bivalente Original/Ómicron BA.1 of Pfizer-BioNTech	Click to see the list
Comirnaty bivalente Original/Ómicron BA.4/BA.5 of Pfizer-BioNTech New	Click to see the list
Convidecia; PackVac of CanSino	Click to see the list
Corbevax of Biological E Limited	India
CoronaVac of Sinovac Research and Development	Click to see the list
Covaxin (BBV152) of Bharat Biotech	Click to see the list
Covifenz of Medicago	Canada
Covilo of Beijing Institute of Biological Products; China National Pharmaceutical Group (Sinopharm)	Click to see the list
CovIran Barekat of Shifa Pharmed Industrial Group	Iran
Covishield of Serum Institute of India	Click to see the list
Covovax (Novavax formulation) of Serum Institute of India	Click to see the list
EpiVacCorona of Vector State Research Center of Virology and Biotechnology	Click to see the list
Fakhravac (MIVAC) of Organization of Defensive Innovation and Research	Iran
Gam-COVID-Vac of Gamaleya	Russia
Gemcovac-19 of Gennova Biopharmaceuticals	India
Inactivated vaccine of Chinese Academy of Medical Sciences	China
Incovacc of Bharat Biotech	Click to see the list
Jcovden (Ad26.COV2.S) of Janssen (Johnson & Johnson)	Click to see the list
Kconvac of Minhai Biotechnology Co	China; Indonesia
KoviVac of Chumakov Center	Russia; Belarus; Cambodia
Mvc-cov1901 of Medigen	Paraguay; Somaliland; Taiwan
Noora of Baqiyatallah University of Medical Sciences	Iran
Nuvaxovid of Novavax	Click to see the list
QazVac of Research Institute for Biological Safety Problems (RIBSP)	Kazakhstan; Kyrgyzstan
Razi Cov Pars of Razi Vaccine and Serum Research Institute	Iran
Recombinant SARS-CoV-2 Vaccine (CHO Cell) of National Vaccine and Serum Institute	United Arab Emirates
Skycovione of SK Bioscience	Corea del sur
Soberana 02 of Finlay Institute of Vaccines	Click to see the list
Soberana Plus of Finlay Institute of Vaccines	Click to see the list
Spikevax (mRNA-1273) of Moderna	Click to see the list
Spikevax bivalente Original/Ómicrom BA.1 of Moderna	Click to see the list
Spikevax Original/Ómicrom BA.4/BA.5 of Moderna	Click to see the list
SpikoGen of Vaxine/CinnaGen Co	Iran
Sputnik Light of Gamaleya/	Click to see the list
Sputnik V of Gamaleya	Click to see the list
Tak-019 (Novavax formulation) of Takeda	Japan
Tak-919 (Moderna formulation) of Takeda	Japan
Turkovac of Health Institutes of Turkey	Turkey
V-01 of Livson Mabpharm Inc	China
Valneva Vla2001 of Valneva	Click to see the list
Vaxzevria of AstraZeneca AB	Click to see the list
Vaxzevria of AstraZeneca/ SK Bioscience CO. Ltd	Click to see the list
VidPrevtyn Beta New	European Union (based upon the recommendation of the European Medicines Agency)
WIBP-CorV of Wuhan Institute of Biological Products; China National Pharmaceutical Group (Sinopharm)	Click to see the list
Zifivax of Anhui Zhifei Longcom	Click to see the list
ZyCoV-D of Zydus Cadila	India

Adopted Name	Name	EUL holder and NRA responsable	Authorized sites (Finished product - countries)
Pfizer-BioNTech COVID-19 vaccine 2BNT162b2; Tozinameran; Comirnaty	COMIRNATY® COVID-19 mRNA Vaccine (nucleoside modified)	Holder: BioNTech Manufacturing GmbH, Alemania NRA responsable: European Medicines Agency (EMA) Effective date: 31/12/2020 Reference Link:http://bit.ly/3NwlDFa	Authorized site: EE.UU. NRA Food and Drug Administration (FDA), USA Efective date: 16/7/2021 Reference Link: https://bit.ly/3wPb0Hr
Pfizer-BioNTech COVID-19 vaccine 2BNT162b2; Tozinameran/riltozinameran	COMIRNATY®Original/Omicron BA.1 COVD-19 mRNA Vaccine (nucleoside modified)	Holder: BioNTech Manufacturing GmbH, Alemania NRA responsable: European Medicines Agency (EMA) Effective date: 19/10/2022 Reference Link: https://extranet.who.int/pqweb/vaccines/comirnaty-originalomicron-ba1
Pfizer-BioNTech COVID-19 vaccine Tozinameran/famtozinameran New	COMIRNATY®Original/Omicron BA.4-5 COVD-19 mRNA Vaccine (nucleoside modified)	Holder: BioNTech Manufacturing GmbH, Alemania NRA responsable: European Medicines Agency (EMA) Effective date: 11/11/2022 Reference Link: https://extranet.who.int/pqweb/vaccines/comirnaty-originalomicron-ba4-5
EU Nodes-AstraZeneca/ Oxford COVID-19 vaccine; Vaxzevria in Europe (formerly AZD1222 and ChAdOx1)*	Vaxzevria COVID-19 Vaccine (ChAdOx1-S [recombinant])	Holder: AstraZeneca/SK Bioscience Co. Ltd, Republica de Corea NRA responsable: Ministry of Food and Drug Safety Effective date: 15/2/2021 Reference Link: http://bit.ly/3NxXKNg
EU Nodes-AstraZeneca/ Oxford COVID-19 vaccine; Vaxzevria in Europe (formerly AZD1222 and ChAdOx1)*	Vaxzevria COVID-19 Vaccine (ChAdOx1-S [recombinant])	Holder: AstraZeneca AB NRA responsable: European Medicines Agency EMA Effective date: 15/4/2021 Reference Link: https://bit.ly/3KDGlkr	Authorized sites: (1) Italia, Japón RNA responsable: Ministry of Health, Labour and Welfare, Japon Efective date (1): 09/7/2021 Reference Link site: https://bit.ly/3iQGepq Authorized sites: (2) EE.UU, Italia, Reino Unido, Alemania, Australia, Tailandia RNA responsable: Therapeutic Goods Administration, Australia Efective date (2): 09/7/2021 Reference Link site: https://bit.ly/3wOMhTL Authorized sites: (3) Italia, Reino Unido, Alemania, Australia, EE.UU RNA responsable: Health Canadá Efective date (3): 21/8/2021 Reference Link site: https://bit.ly/3Loo0Ic Authorized sites: (4) Argentina, México RNA responsable: COFEPRIS, México; ANMAT, Argentina Efective date (4): 23/12/2021 Reference Link site: https://bit.ly/3uCVCeB
Serum Institute of India COVID-19 vaccine; Covishield in India*	COVISHIELD™ COVID-19 Vaccine (ChAdOx1-S [recombinant])	Holder: Serum Institute of India Pvt. Ltd. NRA responsable: Central Drugs Standard Control Organization Effective date: 15/4/2021 Reference Link: https://bit.ly/3KDGlkr
Janssen COVID-19 vaccine JNJ-78436735; Ad26.COV2-S (recombinant).	COVID-19 Vaccine (Ad26.COV2-S [recombinant])	Holder: Janssen–Cilag International NV. NRA responsable: European Medicines Agency EMA Effective date: 12/3/2021 Reference Link: https://bit.ly/382QkkW
Moderna COVID-19 vaccine mRNA-1273*	Spikevax COVID-19 mRNA Vaccine (nucleoside modified)	Holder: Moderna Biotech NRA responsable: European Medicines Agency EMA Effective date: 30/4/2021 Reference Link: https://bit.ly/3DsvHum	Authorized sites: República de Korea RNA responsable: Ministry of Food and Drug Safety (MFDS), Republic of Korea Efective date: 23/12/2021 Reference Link: https://bit.ly/3wORR8F
Moderna COVID-19 vaccine mRNA-1273*	Spikevax COVID-19 mRNA Vaccine (nucleoside modified)	Holder: Moderna TX,Inc. RNA responsable: FDA, USA Effective date: 6/8/2021 Reference Link: https://bit.ly/3wR7BrW
Sinopharm/ BIBP COVID-19 vaccine Inactivated SARS-CoV-2-vaccine (Vero cell); BBIBP-CorV	Inactivated COVID-19 Vaccine (Vero Cell)	Titular: Beijing Institute of Biological Products Co., Ltd. (BIBP) ARN responsable: National Medicinal Products Association Effective date: 7/5/2021 Reference Link: https://bit.ly/3K0A56k
Sinovac COVID-19 vaccine CoronaVac; adsorbed COVID-19 vaccine	CoronaVac COVID-19 Vaccine (Vero Cell), Inactivated	Titular: Sinovac Life Sciences Co., Ltd. China ARN responsable: National Medicinal Products Association Effective date: 1/6/2021 Reference Link: https://bit.ly/3NysEFh
Bharat Biotech COVID-19 vaccine; Covaxin; BBV152 Suspension of supply	COVAXIN® Covid-19 vaccine (Whole Virion Inactivated Corona Virus vaccine)	Holder: Bharat Biotech International Limited RNA responsable: Central Drugs Standard Control Organization Effective date: 3/11/2021 Reference Link: https://bit.ly/36EjcQg
Novavax vaccine COVID-19; NVX-CoV2373	COVOVAX™ COVID-19 vaccine (SARS-CoV-2 rS Protein Nanoparticle [Recombinant])	Holder: Serum Institute of India Pvt. Ltd RNA responsable: Central Drugs Standard Control Organization Effective date: 17/12/2021 Reference Link: https://bit.ly/3uAxHwq
Novavax vaccine COVID-19; NVX-CoV2373	NUVAXOVID™ COVID-19 Vaccine (SARS-CoV-2 rS [Recombinant, adjuvanted])	Holder: Novavax CZ a.s RNA responsable: European Medicines Agency EMA Effective date: 20/12/2021 Reference Link: https://bit.ly/3qPVFmp
COVID-19 Vaccine, (Ad5.CoV2-S [Recombinant])	Convidecia COVID-19 Vaccine, (Ad5.CoV2-S [Recombinant])	Holder: CanSino Biologics Inc. RNA responsable: National Medical Products Administration (NMPA) Effective date: 19 May 2022 Reference Link: https://extranet.who.int/pqweb/vaccines/convidecia

	Anhui Zhifei Longcom COVID-19 vaccine: Zifivax	AstraZeneca/ Oxford; SK BIO; Serum Institute of India COVID-19 vaccine: Vaxzevria; Covishield	Bharat Biotech COVID-19 vaccine: Covaxin (suspended supply)	CanSino COVID-19 vaccine: Convidecia	CIGB COVID-19 vaccine: Abdala	Finlay Institute COVID-19 vaccine: Soberana 02; Soberana Plus	Gamaleya COVID-19 vaccine: Sputnik V; Gam-COVID-Vac; Spuntik Light	Janssen COVID-19 vaccine: Jcovden	Moderna COVID-19 vaccine: Spikevax	Novavax COVID-19 vaccine: Nuvaxovid; Covovax	Pfizer-BioNTech COVID-19 vaccine: Comirnaty	Sinopharm/BIBP COVID-19 vaccine: Covilo	Sinopharm/WIBP COVID-19 vaccine	Sinovac COVID-19 vaccine: CoronaVac	Valneva COVID-19 vaccine	Vector Institute COVID-19 vaccine: EpiVacCorona
Alpha B.1.1.7	88.3% (66.8% to 97.0%) [1]	70% (44% to 84%) [2]	-	-	-	-	-	70.2% (35.3% to 87.6%) [11]	92% (86% to 96%) [15]*	86% (71% to 94%) [19]	83% (69% to 91.3%) to 88% (85% to 90%) [21], [22]*	-	-	65.0% (0% to 75%) [27]*	-	-
Beta B.1.351	-	10% (0% to 55%) [3]	-	-	-	-	-	51.9% (19.1% to 72.2%) [11]	-	51% (0% to 76%) [20]	100% (54% to 100%) [23]	-	-	-	-	-
Gamma P.1	-	63.6% (0.00% to 87.00%) [4]*	-	-	-	-	-	36.5% (14.1% to 53.3%) [11]	-	-	93% (78% to 98%) [22]*	-	-	41.6% (26.9% to 53.3%) [28]*	-	-
Delta B.1.617.2	76.1% (70.0% to 81.2%) [1]	44.3% (43.2% to 45.4%) to 74.5% (23.7% to 51.5%) [5], [6]*	65% (33% to 83%) [8]	61.5% (9.5% to 83.6%) [9]*	-	-	57% (51% to 63%)[10]*	39.3% (36.1% to 42.4%) to 72% (64% to 78%) [12], [13]*	72% (57% to 82%) to 98% (97% to 99%) [15], [16]*	-	62.4% (59.4% to 65.1%) to 95% (93% to 96%) [16], [24]*	63.5% (37.2% to 89.8%) [26]*	-	-	-	-
Omicron B.1.1.529	-	38.5% (20.2% to 52.6%) [7]*	-	-	-	-	-	37.3% (32.9% to 41.5%) [14]*	37.9% (34.4%-41.2%) to 75.1% (70.8% to 78.7%) [17], [18]*	-	37.0% (35.6% to 38.3%) to 91% (83% to 95%) [17], [25]*		-	-0.3% (-2.7 to -2.1) to 77.8% (49.6 to 90.2) [29], [30]*	-	-

	Anhui Zhifei Longcom COVID-19 vaccine: Zifivax [1]	AstraZeneca/ Oxford; SK BIO; Serum Institute of India COVID-19 vaccine: Vaxzevria; Covishield [2]	Bharat Biotech COVID-19 vaccine: Covaxin (suspended supply)[3]	CanSino COVID-19 vaccine: Convidecia [4]	CIGB COVID-19 vaccine: Abdala	Finlay Institute of vaccines COVID-19 vaccine: Soberana 02; Soberana Plus [5]	Gamaleya COVID-19 vaccine: Sputnik V; Gam-COVID-Vac; Spuntik Light [6]	Janssen COVID-19 vaccine: Jcovden [7]	Moderna COVID-19 vaccine: Spikevax [8]	Novavax COVID-19 vaccine: Nuvaxovid; Covovax [9],[10]	Pfizer-BioNTech COVID-19 vaccine: Comirnaty [11]	Sinopharm/BIBP COVID-19 vaccine: Covilo [12]	Sinopharm/WIBP COVID-19 vaccine [13]	Sinovac COVID-19 vaccine: CoronaVac [14],[15]	Valneva COVID-19 vaccine	Vector Institute COVID-19 vaccine: EpiVacCorona
Contracting COVID-19*	75.7% (71% to 80%)	64% (39% to 79%)	77% (65% to 85%)	57% (40% to 70%)	92% (86% to 96%)	71% (59% to 80%)	91% (83% to 95%)	64% (36% to 79%)	93% (90% to 94%)	90% (84% to 93%)	91% (89% to 93%)	74% (61% to 82%)	64% (49% to 75%)	71% (7% to 91%)	Has not been measured or reported	Has not been measured or reported
Symptomatic COVID-19 infection**	75.7% (71% to 80%)	67% (57% to 74%)	68% (47% to 83%)	64% (53% to 72%)	92% (85% to 96%)	Has not been measured or reported	91% (83% to 95%)	64% (36% to 79%)	93% (90% to 94%)	90% (80% to 95%)	91% (89% to 93%)	78% (65% to 86%)	73% (58% to 82%)	71% (7% to 91%)	Has not been measured or reported	Has not been measured or reported
Asymptomatic COVID-19 infection***	Has not been measured or reported	Has not been measured or reported	64% (29% to 82%)	Has not been measured or reported	Has not been measured or reported	Has not been measured or reported	Has not been measured or reported	Has not been measured or reported	57% (50% to 64%)	Has not been measured or reported	Has not been measured or reported	52% (1% to 78%)	Has not been measured or reported	Has not been measured or reported	Has not been measured or reported	Has not been measured or reported
Contracting severe COVID-19	88% (70% to 96%)	91% (7% to 99%)	93% (49% to 99%)	96% (70% to 99%)	94% (59% to 99%)	78% (41% to 78%)	99% (87% to 100%)	77% (41% to 91%)	98% (92% to 100%)	93% (46% to 99%)	96% (68% to 99%)	80% ( 0% to 99%)	80% ( 0% to 99%)	94% (58% to 99%)	Has not been measured or reported	Has not been measured or reported
Mortality	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****	Not estimated****

COVID-19 vaccines	Other Names	Platform	SAGE/WHO Indication	Administration	Presentation	Diluent	Adjuvant	Preservatives
Anhui Zhifei Longcom COVID-19 vaccine	ZIFIVAX; ZF-UZ-VAC 2001; ZF2001	Protein subunit	Has not been recommended	IM	Monodose vial (0.5 mL)	No	Aluminium hydroxide-based adjuvant	Not yet available
AstraZeneca/Oxford; SK BIO; Serum Institute of India COVID-19 vaccine (EUL)	Vaxzevria in Europe (formerly AZD1222 and ChAdOx1); Covishield in India; ChAdOx1-S [recombinant]	Viral vector (non-replicating)	Individuals aged 18 years and over, pregnancy (if the benefits of vaccination to the pregnant person outweigh the potential risks) and breastfeeding	IM	Multidose vials of 2, 8 or 10 doses (0.5 mL each). Vial volume: 1, 4, or 5 mL, respectively.	No	No	No
Bharat Biotech COVID-19 vaccine (EUL, suspended supply)	Covaxin; BBV152	Inactivated virus	Individuals aged 18 years and over, pregnancy (if the benefits of vaccination to the pregnant person outweigh the potential risks) and breastfeeding.	IM	Monodose (0.5 mL) or multidose vials of 5, 10 and 20 doses (2.5, 5, and 10 mL, respectively).	No	IMDG (Imidazo quinolin gallamide) and alum	Phenoxy ethanol
CanSino COVID-19 vaccine	Convidecia; PakVac; Ad5-nCoV	Viral vector (non-replicating)	Individuals aged 18 years and over, pregnancy (if the benefits of vaccination to the pregnant person outweigh the potential risks) and breastfeeding.	IM	Monodose (0.5 mL) or multidose vials of 3 doses (1,5 mL).	No	No	No
CIGB (Centro de Ingeniería Genética y Biotecnología) COVID-19 vaccine	Abdala; CIGB-66	Protein subunit	Has not been recommended	IM	Multidose vial of 10 doses (0.5 mL each). Vial volume: 5 mL.	No	Aluminium hydroxide-based adjuvant	Thiomersal
Finlay Institute of vaccines COVID-19 vaccine	FINLAY-FR-2, SOBERANA 02; SOBERANA 02 ST; SOBERANA PLUS; SOBERANA PLUS ST	Protein subunit	Has not been recommended	IM	Soberana 02 and Soberana Plus: multidose vial of 10 doses (0.5 mL each). Vial volume: 5 mL. Every 10-dose vial contains thiomersal; Soberana 02 ST and Soberana plus ST: monodose vial without thimerosal.	No	Aluminium hydroxide-based adjuvant	Soberana 02 and Soberana Plus: Thiomersal
Gamaleya COVID-19 vaccine	Sputnik V; Gam-COVID-Vac; Adeno-based (rAd26-S+rAd5-S) / Sputnik light	Viral Vector (non-replicating)	Has not been recommended	IM	Sputnik V: multidose vial of 5 doses (0.5 mL each). Vial volume: 2.5 mL. Sputnik Light: multidose vial of 5 doses (0.5 mL each). Vial volume: 2.5 mL.	No	No	No
Janssen COVID-19 vaccine (EUL)	JCOVDEN; JNJ-78436735; Ad26.COV2-S (recombinant)	Viral vector (non-replicating)	Individuals aged 18 years and over, pregnancy (if the benefits of vaccination to the pregnant person outweigh the potential risks) and breastfeeding	IM	Multidose vial of 5 doses (0.5 mL each). Vial volume: 2.5 mL.	No	No	No
Moderna COVID-19 vaccine (EUL)	Spikevax (original); TAK-919; elasomeran; mRNA-1273	RNA-based vaccine	Individuals aged 6 months and over, pregnancy and breastfeeding.	IM	Multidose vials of 10 or 15 doses (0.5 mL each). Vial volume: 5, or 7.5 mL, respectively.	No	Lipid nanoparticle (LNP)	No
Novavax/Serum Institute of India (SII) COVID-19 vaccine	NUVAXOVID; COVOVAX; NVX-CoV2373	Protein subunit	Individuals aged 12 years and over, pregnancy, and breastfeeding	IM	Multidose vial of 10 doses (0.5 mL each). Vial volume: 5 mL.	No	Matrix-M1	No
Pfizer-BioNTech COVID-19 vaccine (EUL)	Comirnaty; tozinameran; BNT162b2	RNA-based vaccine	Individuals aged 6 months and over, pregnancy and breastfeeding.	IM	Concentrate for dispersion for injection: multidose vial of 6 doses after dilution (0.3 mL each). 'Ready to use' formulation: multi-dose vial (0.3 mL each). Pediatric formulation (5-11 years): concentrate for dispersion for injection: multidose vial of 10 doses after dilution (0.2 mL each).	Concentrate for dispersion for injection: Sodium Chloride. 'Ready to use' formulation: No	Lipid nanoparticle (LNP)	No
Sinopharm/BIBP (Beijing Institute of Biological Products) COVID-19 vaccine (EUL)	Covilo; Inactivated SARS-CoV-2-vaccine (Vero cell); BBIBP-CorV; adsorbed COVID-19 vaccine	Inactivated virus	Individuals aged 18 years and over, pregnancy (if the benefits of vaccination to the pregnant person outweigh the potential risks) and breastfeeding	IM	Monodose (0.5 mL) or multidose vial of 2 or 5 doses (1, or 2.5 mL).	No	Aluminium hydroxide-based adjuvant	No
Sinopharm/WIBP (Wuhan Institute of Biological Products) COVID-19 vaccine	Inactivated SARS-CoV-2-vaccine (Vero cell); WIBP-CorV; adsorbed COVID-19 vaccine	Inactivated virus	Has not been recommended	IM	Monodose vial (0.5 mL)	No	Aluminium hydroxide-based adjuvant	No
Sinovac COVID-19 vaccine (EUL)	CoronaVac; adsorbed COVID-19 vaccine	Inactivated virus	Individuals aged 18 years and over, pregnancy (if the benefits of vaccination to the pregnant person outweigh the potential risks) and breastfeeding	IM	(a) Monodose (0.5 mL) or multidose vial of 2 doses (vial volume: 1 mL), or (b) monodose in a prefilled syringe.	No	Aluminium hydroxide-based adjuvant	No
Vector Institute COVID-19 vaccine	EpiVacCorona; EpiVakKorona	Protein subunit	Has not been recommended	IM	Not yet available	No	No	No
Valneva COVID-19 vaccine	COVID-19 vaccine (inactivated, adjuvanted, adsorbed); VLA2001	Inactivated virus	Individuals aged 18-50 years, pregnancy (if the benefits of vaccination to the pregnant person outweigh the potential risks) and breastfeeding	IM	Multidose vial of 10 doses (0.5 mL each). Vial volume: 5 mL.	No	Aluminium hydroxide-based adjuvant	No

	Myocarditis/pericarditis	Guillain-Barré Syndrome (GBS)	Thrombosis with thrombocytopenia syndrome (TTS)	Capillary leak syndrome (CLS)	Cerebral venous sinus thrombosis (CVST) without thrombocytopenia	Menstrual disorders	Multisystem inflammatory syndrome (MIS)	Small vessel vasculitis with cutaneous manifestations	Autoimmune Hepatitis (AIH)
AstraZeneca/Oxford; SK BIO; Serum Institute of India COVID-19 vaccine: Vaxzevria; Covishield	NA	Guillain-Barré syndrome (GBS) have been reported very rarely following vaccination with Vaxzevria [21]. The benefits of the vaccine outweigh the risks of GBS [2]; [3].	TTS in some cases accompanied by bleeding, has been observed very rarely following vaccination with Vaxzevria. This includes severe cases ans unusual sites such as cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial thrombosis. Some cases had a fatal outcome. The majority of these cases occurred within the first three weeks following vaccination. The reporting rates after the second dose are lower compared to after the first dose [21]. Vaxzevria is contraindicated in persons who have experienced TTS with previous doses of the vaccine [2].	Very rare cases of capillary leak syndrome (CLS) were reported in the first days after vaccination with Vaxzevria, with fatal outcomes in some people with prior experience of CLS. EMA recommends that persons with a known history of CLS should not be vaccinated with Vaxzevria [5] [21].	Events of cerebrovascular venous and sinus thrombosis (CVST) without thrombocytopenia have been observed very rarely following vaccination with Vaxzevria, mostly within the first four weeks following vaccination. This information should be considered for individuals at increased risk for CVST [3].	NA	NA	NA	NA
Bharat Biotech COVID-19 vaccine: Covaxin (suspended supply)	NA	NA	NA	NA	NA	NA	NA	NA	NA
CanSino COVID-19 vaccine: Convidecia	NA	NA	Very rare cases of thrombosis with thrombocytopenia syndrome (TTS) were reported globally (0.081 cases per 100.000 vaccinees as of December 2021) around 3-30 days following vaccination with CanSino [1].	NA	NA	NA	NA	NA	NA
Janssen COVID-19 vaccine: Jcovden	Reporting of advers events probably increased risks of myocarditis and pericarditis, particularly within the period 0 to 7 days after vaccination [cb18ffd03bac048bbab5482a4784537781c67a3f]	GBS has been reported very rarely following vaccination with Janssen COVID-19 vaccine. As of April 2022, 535 cases were reported globally (1.5 cases per million vaccinees) [6], [18] The benefits of the vaccine outweigh the risks of GBS [6].	Very rare cases of thrombosis with thrombocytopenia syndrome (TTS) were reported following the first dose of Janssen COVID-19 vaccine. As of April 2022, 109 cases were reported globally (2 cases per million vaccinees) [6]. The benefits of vaccination outweigh the risks, especially in older age groups [4]. Janssen COVID-19 vaccine is contraindicated in persons who have experienced TTS with previous doses of the vaccine [4]; [6].	Very rare cases of capillary leak syndrome (CLS) were reported in the first days after vaccination with Janssen COVID-19 vaccine, with fatal outcomes in some people with prior experience of CLS. EMA recommends that persons with a known history of CLS should not be vaccinated with Janssen COVID-19 vaccine [7] [18]	Venous thromboembolism (VTE) has been observed rarely following vaccination with Janssen COVID-19 vaccine. This should be considered for individuals at increased risk for VTE [8].	NA	NA	PRAC/EMA recommends that small vessel vasculitis with cutaneous manifestations should be added to the product information of the Janssen COVID-19 vaccine as a possible side effect with unknown frequency [9].	NA
Moderna COVID-19 vaccine: Spikevax	These conditions can develop within just a few days after vaccination, and have primarily occurred within 14 days. They have been observed more often after the second dose compared to the first dose, and more often in younger males [19]. The benefits of Spikevax continue to outweigh its risks in all age groups [10].	NA	NA	A few cases of capillary leak syndrome (CLS) flare-ups have been reported in the first days after vaccination with Spikevax [19].	NA	The PRAC-EMA has concluded that heavy menstrual bleeding is a side effect of unknown frequency of Spikevax. Most of cases are non-serious and temporaty in nature. There is no evidence to suggest the menstrual disorders experienced have any impact on reproduction and fertility [12].	NA	NA	According to PRAC/EMA, the available evidence does not support a causal link between Moderna COVID-19 vaccine and very rare cases of autoimmune hepatitis (AIH) [13].
Novavax COVID-19 vaccine: Nuvaxovid; Covovax	There is an increased risk of myocarditis and pericarditis following vaccination with Nuvaxovid. These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days. [16].	NA	NA	NA	NA	NA	NA	NA	NA
Pfizer-BioNTech COVID-19 vaccine: Comirnaty	There is an increased risk of myocarditis and pericarditis following vaccination with Comirnaty. These conditions can develop within just a few days after vaccination, and have primarily occurred within 14 days. They have been observed more often after the second vaccination, and more often in younger males; [14], [17]. The benefits of Comirnaty continue to outweigh its risks in all age groups [14].	NA	NA	NA	NA	The PRAC-EMA has concluded that heavy menstrual bleeding is a side effect of unknown frequency of Comirnaty. Most of cases are non-serious and temporaty in nature. There is no evidence to suggest the menstrual disorders experienced have any impact on reproduction and fertility [17].	According to PRAC/EMA, there is currently insufficient evidence of a possible link between Comirnaty and very rare cases of multisystem inflammatory syndrome (MIS) [15].	NA	According to PRAC-EMA, the available evidence does not support a causal link between Comirnaty and very rare cases of autoimmune hepatitis (AIH) [13].
Sinopharm/BIBP COVID-19 vaccine: Covilo	NA	NA	NA	NA	NA	NA	NA	NA	NA
Sinovac COVID-19 vaccine: CoronaVac	NA	NA	NA	NA	NA	NA	NA	NA	NA

	Individuals 6 months to 4 years old	Individuals 5 to 11 years old	Individuals 12 to 17 years old	Individuals 18 years old and older	Pregnant and breastfeeding women	Immunocompromised persons (moderate and severe)				Heterologous scheme	Booster doses
	Individuals 6 months to 4 years old	Individuals 5 to 11 years old	Individuals 12 to 17 years old	Individuals 18 years old and older	Pregnant and breastfeeding women	6 months to 4 years old	5 to 11 years old	12 to 17 years old	18 years and older	Heterologous scheme	Booster doses
Anhui Zhifei Longcom COVID-19 vaccine: Zifivax (Authorized) [1]	Not recommended yet	Not recommended yet	Not recommended yet	INVIMA/Colombia: Three doses (0.5 mL each) 4 and 8 weeks apart.	INVIMA/Colombia: contraindicated in pregnant women.	Not recommended yet	Not recommended yet	Not recommended yet	INVIMA/Colombia: primary series of three doses (0.5 mL each) 4 and 8 weeks apart.	There is no available data on interchangeability.	There is no available data on booster doses beyond the third dose.
AstraZeneca/Oxford; AstraZeneca/SK BIO; Serum Institute of India COVID-19 vaccine: Vaxzevria; Covishield (EUL/WHO authorization) [2]	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: Two doses (0.5 mL each) 4 to 12 weeks apart. WHO recommends an interval of 8 to 12 weeks between doses.	SAGE/WHO: Two doses (0.5 mL each) 8 to 12 weeks apart. WHO recommends using the Vaxzevria/Covishield COVID-19 vaccine in pregnant women only if the benefits of vaccination outweigh the potential risks.	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: Extended primary series with an additional (third) dose of 0.5 mL 1-3 months after the second dose, followed by a booster (fourth) dose provided 3-6 months after.	SAGE/WHO: Vaxzevria/Covishield combined with any other EUL COVID-19 vaccine is considered a complete primary series.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series* using any other EUL vaccine (preferably an mRNA-based or Novavax vaccine).
Bharat Biotech COVID-19 vaccine: Covaxin (EUL/WHO authorization, suspended supply) [3]	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: Two doses (0.5 mL each) 4 weeks apart.	SAGE/WHO: Two doses (0.5 mL each) 4 weeks apart. WHO recommends using the Bharat Biotech COVID-19 vaccine in pregnant women only if the benefits of vaccination outweigh the potential risks.	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: Extended primary series with an additional (third) dose of 0.5 mL 1-3 months after the second dose, followed by a booster (fourth) dose provided 3-6 months after.	SAGE/WHO: Bharat Biotech COVID-19 vaccine combined with any other EUL COVID-19 vaccine is considered a complete primary series.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series*.
CanSino COVID-19 vaccine: Convidecia (EUL/WHO authorization) [4]	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: One dose of 0.5 mL.	SAGE/WHO: One dose of 0.5 mL. WHO recommends using the CanSino COVID-19 vaccine in pregnant women only if the benefits of vaccination outweigh the potential risks.	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: Extended primary series with an additional (second) dose administered 1-3 months after the first dose.	SAGE/WHO: CanSino COVID-19 vaccine may be used as a booster dose following a primary series using any other EUL COVID-19 vaccine.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series*.
CIGB COVID-19 vaccine: Abdala (Authorized) [5]	CECMED/Cuba: 2 years of age and older. Three doses (0.5 mL) 2 weeks apart.	CECMED/Cuba: Three doses (0.5 mL) 2 weeks apart.	CECMED/Cuba: Three doses (0.5 mL) 2 weeks apart.	CECMED/Cuba: Three doses (50 µg, 0.5 mL) 2 weeks apart.	CECMED/Cuba: if the benefits of the vaccination outweigh the potential risks.	CECMED/Cuba: 2 years of age and older. Three doses (0.5 mL) 2 weeks apart.	CECMED/Cuba: Three doses (0.5 mL) 2 weeks apart.	CECMED/Cuba: Three doses (0.5 mL) 2 weeks apart.	CECMED/Cuba: Three doses (50 µg, 0.5 mL) 2 weeks apart.	There is no available data on interchangeability.	There is no available data on booster doses.
Finlay Institute of Vaccines COVID-19 vaccine: Soberana 02; Soberana Plus (Authorized) [6]	CECMED/Cuba: SOBERANA 02 and SOBERANA 02 ST: 2 years of age and older. Two doses (0.5 mL) 4 weeks apart. SOBERANA PLUS and SOBERANA PLUS as a booster dose 4 weeks after.	CECMED/Cuba: SOBERANA 02 and SOBERANA 02 ST: Two doses (0.5 mL) 4 weeks apart. SOBERANA PLUS and SOBERANA PLUS as a booster dose 4 weeks after.	CECMED/Cuba: SOBERANA 02 and SOBERANA 02 ST: Two doses (0.5 mL) 4 weeks apart. SOBERANA PLUS and SOBERANA PLUS as a booster dose 4 weeks after.	CECMED/Cuba: SOBERANA® 02 and SOBERANA® 02 ST: Two doses (0.5 mL each) 4 weeks apart. Soberana Plus and Soberana Plus ST: Single dose (0.5 mL) as a booster vaccine 4 weeks after a primary schedule with SOBERANA® 02 or SOBERANA® 02 ST.	CECMED/Cuba: if the benefits of the vaccination outweigh the potential risks.	CECMED/Cuba: SOBERANA 02 and SOBERANA 02 ST: 2 years of age and older. Two doses (0.5 mL) 4 weeks apart. SOBERANA PLUS and SOBERANA PLUS as a booster dose 4 weeks after.	CECMED/Cuba: SOBERANA 02 and SOBERANA 02 ST: Two doses (0.5 mL) 4 weeks apart. SOBERANA PLUS and SOBERANA PLUS as a booster dose 4 weeks after.	CECMED/Cuba: SOBERANA 02 and SOBERANA 02 ST: Two doses (0.5 mL) 4 weeks apart. SOBERANA PLUS and SOBERANA PLUS as a booster dose 4 weeks after.	CECMED/Cuba: SOBERANA® 02 and SOBERANA® 02 ST: Two doses (0.5 mL each) 4 weeks apart. Soberana Plus and Soberana Plus ST: Single dose (0.5 mL) as a booster vaccine 4 weeks after a primary schedule with SOBERANA® 02 or SOBERANA® 02 ST.	There is no available data on interchangeability.	CECMED/Cuba: SOBERANA Plus and SOBERANA Plus ST may be used as a booster dose 4 weeks after a primary schedule with SOBERANA 02 or SOBERANA 02 ST.
Gamaleya COVID-19 vaccine: Sputnik V; Gam-COVID-Vac; Spuntik Light (Authorized) [7],[8]	Not recommended yet	Not recommended yet	Not recommended yet	ANMAT/Argentina: Sputnik V: Two doses of different components (0,5ml each) 3 weeks apart. Sputnik Light: One dose (0.5 mL).	ISP/Chile: if the benefits of the vaccination outweigh the potential risks.	Not recommended yet	Not recommended yet	Not recommended yet	ANMAT/Argentina: primary schedule with Sputnik V, followed by an additional (third) dose 4 months after with Sputnik V.	ANMAT/Argentina: a heterologous scheme using Sputnik V component 1 followed by a second dose of any authorized mRNA-based or viral vector vaccine may be used.	ANMAT/Argentina: A booster dose should be given at least 4 months after the primary scheme using an mRNA-based or viral vector vaccine.
Janssen COVID-19 vaccine: Jcovden (EUL/WHO authorization) [9]	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: One or two doses (0.5 mL each). WHO recommends providing two doses with an interval of 2 to 6 months.	SAGE/WHO: One or two doses (0.5 mL each) 2-6 months apart. WHO recommends using the Janssen COVID-19 vaccine in pregnant women only if the benefits of vaccination outweigh the potential risks.	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: Two doses (0.5 mL each) 1-3 months apart.	SAGE/WHO: the homologous two-dose schedule is the standard practice. However, a heterologous scheme using a second dose of an mRNA vaccine may be more immunogenic and effective.	SAGE/WHO: the need and timing of booster doses beyond the second dose are under assessment.
Moderna COVID-19 vaccine: Spikevax (EUL/WHO authorization) [10]	SAGE/WHO: for ages 6 months-5 years: Two doses (25 µg, 0.25 ml each) 4-8 weeks apart.	SAGE/WHO: ages 6-11 years: Two doses (50 µg each) 4-8 weeks apart.	SAGE/WHO: Two doses (100 µg, 0.5 ml each) 4 to 8 weeks apart.	SAGE/WHO: Two doses (100 µg, 0.5 ml each) 4 to 8 weeks apart.	SAGE/WHO: Two doses (100 µg, 0.5 mL each) 8 weeks apart.	SAGE/WHO: Extended primary series with an additional (third) dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Extended primary series with an additional (third) dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Extended primary series with an additional (third) dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Extended primary series with an additional (third) dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Moderna COVID-19 vaccine combined with any other EUL COVID-19 vaccine is considered a complete primary series.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series* and a second booster after 4-6 months for specific population groups**. WHO recommends Moderna COVID-19 vaccine as a heterologous booster.
Novavax/ Serum Institute of India COVID-19 vaccine: Nuvaxovid; Covovax (EUL/WHO authorization) [11], [12]	Not recommended yet	Not recommended yet	SAGE/WHO: Two doses (0.5 mL each) 3-4 weeks apart.	SAGE/WHO: Two doses (0.5 mL each) 3-4 weeks apart.	SAGE/WHO: Two doses (0.5 mL each) 3-4 weeks apart.	Not recommended yet	Not recommended yet	SAGE/WHO: Extended primary series with an additional (third) dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Extended primary series with an additional (third) dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Novavax COVID-19 vaccine combined with any other EUL COVID-19 vaccine is considered a complete primary series.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series* and a second booster after 4-6 months for specific population groups**.
Pfizer-BioNTech COVID-19 vaccine: Comirnaty (EUL/WHO authorization) [13]	SAGE/WHO: Three doses (3 µg, 0.2 each). The first two doses administered 3 weeks apart, followed by a third dose 8 weeks after.	SAGE/WHO: Two doses (10 µg, 0.2 mL each) 4 to 8 weeks apart.	SAGE/WHO: Two doses (30 µg, 0.3 mL each) 4 to 8 weeks apart.	SAGE/WHO: Two doses (30 µg, 0.3 mL each) 4 to 8 weeks apart. WHO recommends an interval of 8 weeks.	SAGE/WHO: Two doses (30 µg, 0.3 mL each) 8 weeks apart.	SAGE/WHO: Three doses (3 µg, 0.2 each), and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Extended primary series with an additional (third) 10 µg dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Extended primary series with an additional (third) 30 µg dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Extended primary series with an additional (third) 30 µg dose 1-3 months after the second dose, and two boosters (fourth and fifth doses) given 4-6 months after the previous dose.	SAGE/WHO: Comirnaty (Pfizer-BioNTech) combined with any other EUL COVID-19 vaccine is considered a complete primary series.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series* and a second booster after 4-6 months for specific population groups**. WHO recommends Comirnaty vaccine as a heterologous booster.
Sinopharm/BIBP COVID-19 vaccine: Covilo (EUL/WHO authorization) [7], [14]	ANMAT/Argentina: 3 years of age and older. Two doses (0.5 mL each) 3 weeks apart.	ANMAT/Argentina: Two doses (0.5 mL each) 3 weeks apart.	ANMAT/Argentina: Two doses (0.5 mL each) 3 weeks apart.	SAGE/WHO: Two doses (0.5mL each) 3 weeks apart. WHO recommends an interval of 3-4 weeks.	SAGE/WHO: Two doses (0.5 mL each) 3 to 4 weeks apart. WHO recommends using the Sinopharm/BIBP COVID-19 vaccine in pregnant women only if the benefits of vaccination outweigh the potential risks.	ANMAT/Argentina: 3 years of age and older. Two doses (0.5 mL) 3 weeks apart, followed by an additional (third) dose provided 4 weeks after.	ANMAT/Argentina: Two doses (0.5 mL) 3 weeks apart, followed by an additional (third) dose provided 4 weeks after.	ANMAT/Argentina: Two doses (0.5 mL) 3 weeks apart, followed by an additional (third) dose provided 4 weeks after.	SAGE/WHO: Extended primary series with an additional (third) dose of 0.5 mL 1-3 months after the second dose, followed by a booster (fourth) dose provided 3-6 months after.	SAGE/WHO: Sinopharm/BIBP COVID-19 vaccine combined with any other EUL COVID-19 vaccine is considered a complete primary series.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series* using any other EUL vaccine (preferably an mRNA-based or viral vector vaccine).
Sinopharm/WIBP COVID-19 vaccine (Authorized) [15], [16]	Not recommended yet	Not recommended yet	Not recommended yet	NMPA/China: Two doses (0.5mL each) 3-4 weeks apart.	NMPA/China: There is insufficient data on using the Sinopharm/WIBP COVID-19 vaccine during pregnancy.	Not recommended yet	Not recommended yet	Not recommended yet	NMPA/China: Two doses (0.5mL each) 3-4 weeks apart.	NMPA/China: a heterologous booster schedule is recommended.	NMPA/China: A booster dose should be given 6 months after the primary series using a protein subunit vaccine (Anhui Zhifei vaccine) or a viral vector-based one (CanSino vaccine).
Sinovac COVID-19 vaccine: CoronaVac (EUL/WHO authorization) [8], [17]	ISP/Chile: Two doses 2-4 weeks apart (dosage recommendation not yet available)	ISP/Chile: Two doses (0.5 mL) 2-4 weeks apart.	ISP/Chile: Two doses (0.5 mL) 2-4 weeks apart.	SAGE/WHO: Two doses (0.5 mL each) 2-4 weeks apart. WHO recommends an interval of 4 weeks.	SAGE/WHO: Two doses (0.5 mL each) 2-4 weeks apart. WHO recommends using the Sinovac COVID-19 vaccine in pregnant women only if the benefits of vaccination outweigh the potential risks.	ISP/Chile: recommendation not yet available	ISP/Chile: 3 years of age and older. Two doses (0.5 mL) 2-4 weeks apart and a booster (third) dose provided 2 months after.	ISP/Chile: Two doses (0.5 mL) 2-4 weeks apart and a booster (third) dose provided 2 months after.	SAGE/WHO: Extended primary series with an additional (third) dose of 0.5 mL 1-3 months after the second dose, followed by a booster (fourth) dose provided 3-6 months after.	SAGE/WHO: CoronaVac (Sinovac) combined with any other EUL COVID-19 vaccine is considered a complete primary series.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series* using any other EUL vaccine (preferably an mRNA-based or viral vector vaccine).
Valneva COVID-19 vaccine (Authorized) [18]	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: Two doses (0.5 mL each) 4 weeks apart.	SAGE/WHO: Two doses (0.5 mL each) 4 weeks apart. WHO recommends using the Valneva COVID-19 vaccine in pregnant women only if the benefits of vaccination outweigh the potential risks.	Not recommended yet	Not recommended yet	Not recommended yet	SAGE/WHO: Extended primary series with an additional (third) dose of 0.5 mL 1-3 months after the second dose, followed by a booster (fourth) dose provided 4-6 months after.	SAGE/WHO: Valneva COVID-19 vaccine may be used as a booster dose following a primary series using Vaxzevria or Covishield.	SAGE/WHO: A booster dose should be given 4-6 months after the primary series* using any other EUL vaccine.
Vector Institute COVID-19 vaccine: EpiVacCorona (Authorized) [19]	Not recommended yet	Not recommended yet	Not recommended yet	Ministry of Health/Russian Federation: Two doses (0.5 mL) 3 weeks apart.	Ministry of Health/Russian Federation: contraindicated in pregnant women.	Not recommended yet	Not recommended yet	Not recommended yet	Ministry of Health/Russian Federation: Two doses (0.5 mL) 3 weeks apart.	There is no available data on interchangeability.	There is no available data on booster doses.

Topics	Main advisory stakeholders	AstraZeneca/ Oxford; SK BIO; Serum Institute of India COVID-19 vaccine: Vaxzevria; Covishield	Bharat Biotech COVID-19 vaccine: Covaxin (suspended supply)	CanSino COVID-19 vaccine: Convidecia	Janssen COVID-19 vaccine: Jcovden	Moderna COVID-19 vaccine: Spikevax	Novavax COVID-19 vaccine: Nuvaxovid; Covovax	Pfizer-BioNTech COVID-19 vaccine: Comirnaty	Sinopharm/BIBP COVID-19 vaccine: Covilo	Sinovac COVID-19 vaccine: CoronaVac
Efficacy against symptomatic COVID-19 in adults (95% CI)	Strategic Advisory Group of Experts on Immunization (SAGE)	72% (63-79%) *against confirmed COVID-19 [WHO, 2022 ].	78% (65-86%) *against confirmed COVID-19 [WHO, 2022 ].	58% (40-70%) *against confirmed COVID-19 [WHO, 2022 ].	Single dose: 67% (59-73%). Two doses: 75% (55-87%) [WHO, 2022 ].	93% (91-95%) *against confirmed COVID-19 [WHO, 2022 ].	90% (80-95%) *against confirmed COVID-19 [WHO, 2022 ].	91% (89-93%) **persons >16 years [WHO, 2022 ].	79% (66-87%) *against confirmed COVID-19 [WHO, 2022 ].	51% (36-62%) [WHO, 2022 ].
Efficacy against symptomatic COVID-19 in adults (95% CI)	Global Advisory Committee on Vaccine Safety (GACVS)	NA	NA	NA	NA	NA	NA	NA	NA	NA
Efficacy against symptomatic COVID-19 in adults (95% CI)	Technical Advisory Group (TAG)	>76% [TAG, 2022 ].	>64% [TAG, 2022 ].	NA	>67% [TAG, 2022 ].	>93% [TAG, 2022 ].	>90% [TAG, 2022 ].	>95% [TAG, 2022 ].	>79% [TAG, 2022 ].	>67% [TAG, 2022 ].
Efficacy against symptomatic COVID-19 in adults (95% CI)	Centers for Disease Control and Prevention (CDC)	NA	NA	NA	66% (60-71%) [CDC, 2021 ].	94.1% (89.3-96.8%) [CDC, 2020 ].	89.6% (82.4-93.8%) [Twentyman E, 2022 ]	95.0% (90.3-97.6%) **persons >16 years [CDC, 2020 ].	NA	NA
Efficacy against symptomatic COVID-19 in adults (95% CI)	Food and Drug Administration (FDA)	NA	NA	NA	66.9% (59.0-73.4%) [FDA, 2021 ].	94.1% (89.3-96.8%) [FDA, 2022 ].	NA	95.0% (90.3-97.6%) **persons >16 years [FDA, 2022 ].	NA	NA
Efficacy against symptomatic COVID-19 in adults (95% CI)	European Medicines Agency (EMA)	74.0% (65.3-80.5%) [EMA, 2022 ].	NA	NA	66.9% (59.0-73.4%) [EMA, 2022 ].	94.1% (89.3-96.8%) [EMA, 2022 ].	90.4% (82.9-94.6%) [EMA, 2022 ].	95% **persons >16 years [EMA, 2022 ].	NA	NA
Efficacy against symptomatic COVID-19 in adults (95% CI)	Regulatory Authority MHRA/UK	66.7% (57.4-74.0%) [MHRA, 2022 ].	NA	NA	66.9% (59.0-73.4%) [MHRA, 2022 ].	94.1% (89.3-96.8%) [MHRA, 2022 ].	NA	95.0% (90.3-97.6%) [MHRA, 2022 ].	NA	NA
Efficacy against symptomatic COVID-19 in children and adolescents (95% CI)	Strategic Advisory Group of Experts on Immunization (SAGE)	Ongoing studies. Data not yet available [WHO, 2022 ].	Ongoing studies. Data not yet available [WHO, 2022 ].	Ongoing studies. Data not yet available [WHO, 2022 ].	Ongoing studies. Data not yet available [WHO, 2022 ].	Ages 12 to 17: 93% (48-100%) [WHO, 2022 ].	80% (95% CI: 47-92) [WHO, 2022 ].	Ages 5 to 11: 90.7% (67.7-98.3%). Ages 12 to 15: 100% (75-100%) [WHO, 2022 ].	Ongoing studies. Data not yet available [WHO, 2022 ].	Ongoing studies. Data not yet available [WHO, 2022 ].
Efficacy against symptomatic COVID-19 in children and adolescents (95% CI)	Global Advisory Committee on Vaccine Safety (GACVS)	NA	NA	NA	NA	NA	NA	NA	NA	NA
Efficacy against symptomatic COVID-19 in children and adolescents (95% CI)	Technical Advisory Group (TAG)	NA	NA	NA	NA	NA	NA	NA	NA	NA
Efficacy against symptomatic COVID-19 in children and adolescents (95% CI)	Centers for Disease Control and Prevention (CDC)	NA	NA	NA	NA	6 months to 5 years of age: 37.8% (20.9-51.1%) [CDC, 2022 ].	NA	6 months to 4 years of age: 80.0% (22.8-94.8%) [CDC, 2022 ].	NA	NA
Efficacy against symptomatic COVID-19 in children and adolescents (95% CI)	Food and Drug Administration (FDA)	NA	NA	NA	NA	6 to 23 months of age: 31.5% (27.7-62.0%). 2 to 5 years of age: 46.4%. (19.8-63.8%) [FDA, 2022 ].	NA	Ages 5 to 11: 90.7% (67.7-98.3%) Ages 12 to 15: 100% (78.1-100%) [FDA, 2022 ].	NA	NA
Efficacy against symptomatic COVID-19 in children and adolescents (95% CI)	European Medicines Agency (EMA)	Data not yet available [EMA, 2022 ].	NA	NA	Data not yet available [EMA, 2022 ].	In age groups from 6 to 17 years the efficacy is similar to that in adults [EMA, 2022 ].	Ages 12 to 17: 79.5% (46.8-92.1%) [EMA, 2022 ].	Ages 5 to 11: 90.7% (67.7-98.3%) Ages 12 to 15: 100% (75-100%) [EMA, 2022 ].	NA	NA
Efficacy against symptomatic COVID-19 in children and adolescents (95% CI)	Regulatory Authority MHRA/UK	Data not yet available [MHRA, 2022 ].	NA	NA	Data not yet available [MHRA, 2022 ].	Data not yet available [MHRA, 2022 ].	NA	Ages 5 to 11: 90.7% (67.7-98.3%) Ages 12 to 15: 100% (75.3-100.0%) [MHRA, 2022 ].	NA	NA
Vaccination during pregnancy	Strategic Advisory Group of Experts on Immunization (SAGE)	Recommended if the benefits of vaccination outweigh the potential risks [WHO, 2022 ].	Recommended if the benefits of vaccination outweigh the potential risks [WHO, 2022 ].	Recommended if the benefits of vaccination outweigh the potential risks [WHO, 2022 ].	Recommended if the benefits of vaccination outweigh the potential risks [WHO, 2022 ].	Recommended [WHO, 2022 ].	Recommended [WHO, 2022 ].	Recommended [WHO, 2022 ].	Recommended if the benefits of vaccination outweigh the potential risks [WHO, 2022 ].	Recommended if the benefits of vaccination outweigh the potential risks [WHO, 2022 ].
Vaccination during pregnancy	Global Advisory Committee on Vaccine Safety (GACVS)	NA	NA	NA	NA	NA	NA	NA	NA	NA
Vaccination during pregnancy	Technical Advisory Group (TAG)	Recommended [TAG, 2022 ].	Recommended if the benefits of vaccination outweigh the potential risks [TAG, 2022 ].	NA	Recommended [TAG, 2022 ].	Recommended [TAG, 2022 ].	Recommended if the benefits of vaccination outweigh the potential risks [TAG, 2022 ].	Recommended [TAG, 2022 ].	Recommended [TAG, 2022 ].	Recommended [TAG, 2022 ].
Vaccination during pregnancy	Centers for Disease Control and Prevention (CDC)	NA	NA	NA	Recommended [CDC, 2022 ].	Recommended [CDC, 2022 ].	NA	Recommended [CDC, 2022 ].	NA	NA
Vaccination during pregnancy	Food and Drug Administration (FDA)	NA	NA	NA	Available data are insufficient to inform vaccine-associated risks in pregnancy [FDA, 2021 ].	Available data are insufficient to assess the vaccine-associated risks in pregnancy [FDA, 2022 ].	NA	Available data are insufficient to inform vaccine-associated risks in pregnancy [FDA, 2022 ].	NA	NA
Vaccination during pregnancy	European Medicines Agency (EMA)	Recommended if the benefits of vaccination outweigh the potential risks [EMA, 2022 ].	NA	NA	Recommended if the benefits of vaccination outweigh the potential risks [EMA, 2022 ].	Recommended [EMA, 2022 ].	Recommended if the benefits of vaccination outweigh the potential risks [EMA, 2022 ].	Recommended [EMA, 2022 ].	NA	NA
Vaccination during pregnancy	Regulatory Authority MHRA/UK	Recommended if the benefits of vaccination outweigh the potential risks [MHRA, 2022 ].	NA	NA	Recommended if the benefits of vaccination outweigh the potential risks [MHRA, 2022 ].	Recommended [MHRA, 2022 ].	NA	Recommended [MHRA, 2022 ].	NA	NA
SARS-CoV-2 variants	Strategic Advisory Group of Experts on Immunization (SAGE)	Delta variant (effectiveness against hospitalization): 92% (95% CI: 75-97%) Alpha variant (effectiveness against hospitalization): 86% (95% CI: 53-96%) [WHO, 2022 ].	Delta variant (efficacy): 65% (95% CI: 33-83%) [WHO, 2022 ].	NA	Beta variant (South Africa, vaccine efficacy -VE-): 52.0%. Gamma variant (Brazil, VE): 68.1%. Omicron variant (South Africa, healthcare workers): effectiveness against COVID-19-related hospitalizations was 55% (95% CI: 22-74) [WHO, 2022 ].	Delta variant (USA, effectiveness): 79.8% (95% CI: 67.4-87.5%), and 94.0% (95% CI: 92.3-95.4%) after a booster dose. Omicron variant (USA, effectiveness): 42.8% (95% CI: 33.8- 50.7%) and 67.9% (95% CI: 65.8-69.9%) after a booster dose [WHO, 2022 ].	Alpha variant (UK, vaccine efficacy -VE-): 86% (95% CI: 71-94); and 94% (95% CI: 82-98) in USA. Beta variant (South Africa, VE): 49% (95% CI: 28-63) during circulation of Beta [WHO, 2022 ].	Omicron variant: effectiveness is lower compared to Delta [WHO, 2022 ].	NA	Gamma and Alpha variants (Chile, effectiveness): 65.9% (95% CI: 65-66%). Delta variant (Chile, effectiveness): 79% (95% CI: 77-81%) for a 3-dose schedule with CoronaVac (Sinovac) [WHO, 2022 ].
SARS-CoV-2 variants	Global Advisory Committee on Vaccine Safety (GACVS)	NA	NA	NA	NA	NA	NA	NA	NA	NA
SARS-CoV-2 variants	Technical Advisory Group (TAG)	Vaccine effectiveness against COVID-19 declines as for six months after a primary series in the context of variants of concern (including Delta and Omicron variants)[TAG, 2022 ].	Vaccine effectiveness against COVID-19 declines as for six months after a primary series in the context of variants of concern (including Delta and Omicron variants)[TAG, 2022 ].	NA	Vaccine effectiveness against COVID-19 declines as for six months after a primary series in the context of variants of concern (including Delta and Omicron variants)[TAG, 2022 ].	Vaccine effectiveness against COVID-19 declines as for six months after a primary series in the context of variants of concern (including Delta and Omicron variants)[TAG, 2022 ].	Vaccine effectiveness against COVID-19 declines as for six months after a primary series in the context of variants of concern (including Delta and Omicron variants [TAG, 2022 ].	Vaccine effectiveness against COVID-19 declines as for six months after a primary series in the context of variants of concern (including Delta and Omicron variants)[TAG, 2022 ].	Vaccine effectiveness against COVID-19 declines as for six months after a primary series in the context of variants of concern (including Delta and Omicron variants)[TAG, 2022 ].	Vaccine effectiveness against COVID-19 declines as for six months after a primary series in the context of variants of concern (including Delta and Omicron variants)[TAG, 2022 ].
SARS-CoV-2 variants	Centers for Disease Control and Prevention (CDC)	NA	NA	NA	NA	Omicron variant (USA): vaccine effectiveness during the BA.2/BA.2.12.2 period was lower than that during the BA.1 period [CDC, 2022 ].	NA	Omicron variant (USA): vaccine effectiveness during the BA.2/BA.2.12.2 period was lower than that during the BA.1 period [CDC, 2022 ].	NA	NA
SARS-CoV-2 variants	Food and Drug Administration (FDA)	NA	NA	NA	NA	Vaccine efficacy among ages 6 months through 5 years was evaluated during the Omicron-predominant period [FDA, 2022 ].	NA	NA	NA	NA
SARS-CoV-2 variants	European Medicines Agency (EMA)	NA	NA	NA	Alpha variant (efficacy): 71.6% (95% CI: 43.2; 86.9) after the first dose, and 94.2% (95% CI: 62.9; 99.9) after a second dose [EMA, 2022 ].	NA	The vaccine efficacy in adults was assessed while Alpha, Beta, and Gamma was circulating; in ages 12 to 17, during the Delta variant-predominant period [EMA, 2022 ].	NA	NA	NA
SARS-CoV-2 variants	Regulatory Authority MHRA/UK	NA	NA	NA	NA	NA	NA	NA	NA	NA

Vaccine characteristics	Moderna COVID-19 vaccine [1]	Moderna COVID-19 vaccine, bivalent (original + omicron BA.1)	Moderna COVID-19 vaccine, bivalent (original + omicron BA.4/BA.5)	Pfizer-BioNTech COVID-19 vaccine [4]	Pfizer-BioNTech COVID-19 vaccine, bivalent (original + omicron BA.1)	Pfizer-BioNTech COVID-19 vaccine, bivalent (original + omicron BA.4/BA.5)
Name	Spikevax (original)	Spikevax bivalent (original + omicron BA.1)	Spikevax bivalent (original + omicron BA.4/BA.5)	Comirnaty (original)	Comirnaty bivalent (original + omicron BA.1)	Comirnaty bivalent (original + omicron BA.4/BA.5)
International Nonproprietary Name (INN)	elasomeran	elasomeran + imelasomeran	elasomeran + davesomeran	tozinameran	tozinameran+riltozinameran	tozinameran+famtozinameran
Strain/lineage	SARS-CoV-2 Wuhan-Hu-1 strain (Original)	Original and omicron BA.1 [2]	Original and omicron BA.4/BA.5 [2],[3]	SARS-CoV-2 Wuhan-Hu-1 strain (Original)	Original and Omicron BA.1 [5]	Original and Omicron BA.4/BA.5 [7]
Indication	Primary schedule and booster dose for persons 6 months of age and older	EMA: Booster dose for persons from 6 years of age [2].	EMA: Booster dose for persons from 12 years of age [2], FDA: Booster dose for persons from 6 months of age [3].	Primary schedule and booster dose for persons 6 months of age and older.	WHO: Booster dose for persons from 12 years of age [5].	WHO: Booster dose for persons from 12 years of age [7], FDA: for persons from 6 months of age [8].
Dosing and schedule	According to age: - 6 months to 5 years: two doses (25 µg /0.25 mL each) 4 weeks apart. - 6 to 11 years: two doses (50 µg /0.5 mL each) 4 weeks apart. - 12 years and above: two doses (100 µg /0.5 mL each) 4 weeks apart*	According to age: - 6-11 years: EMA: single booster dose (0.25 mL) after three months of the primary series or monovalent booster [2]. - ≥12 years: EMA: single booster dose (0.5 mL) after three months of the primary series or monovalent booster [2].	According to age: - 6 months-5 years: FDA: single booster dose (0.2 mL) after two months of the primary series [3]. 6-11 years: FDA: single booster dose (0.25 mL) after two months of the primary series or monovalent booster [3]. - ≥12 years: FDA: single booster dose (0.5 mL) after two months of the primary series or monovalent booster [3]. EMA recommends an interval of three months [2].	According to age: - 6 months to 4 years: three doses (3 µg /0.2 mL each). The first two doses 3 weeks apart followed by a third dose 8 weeks after. - 5 to 11 years: two doses (10 µg /0.2 mL each) 4 weeks apart. - 12 years and above: two doses (30 µg /0.3 mL each) 4 weeks apart*	EMA: Single booster dose (0.3 mL) for persons ≥12 years after three months of the primary series or monovalent booster [6].	According to age: - 6 months-4 years: FDA: third primary series dose (0.2 mL) after 8 weeks of two monovalent doses [8], and single booster dose (0.2 mL) after two months [9]. - 5-11 years: FDA: single booster dose (0.2 mL) after two months of the primary series or monovalent booster [8]. - ≥12 years: FDA: single booster dose (0.3 mL) after two months of the primary series or monovalent booster [8]. EMA recommends an interval of three months [6].
Presentation of the vial	Light blue border label: 100 µg / 0.5 mL Purple border label: 50 µg / 0.5 mL Magenta border label: 25 µg / 0.25 mL	25 µg elasomeran and 25 µg imelasomeran each dose of 0.5 mL	25 µg elasomeran and 25 µg davesomeran each dose of 0.5 mL	Purple cap: 30 µg / 0.3 mL, after dilution. Grey cap: 30 µg / 0.3 mL Orange cap: 10 µg / 0.2 mL, after dilution. Maroon cap: 3 µg / 0.2 mL, after dilution.	15 µg tozinameran and 15 µg riltozinameran each dose of 0.3 mL	15 µg tozinameran and 15 µg famtozinameran each dose of 0.3 mL

Bharat Biotech COVID-19 vaccine

Bharat Biotech COVID-19 vaccine

Bharat Biotech International Limited

Authorization

Regulatory Authorities of Regional Reference in the Americas

Manufacturing

General characteristics

Risk considerations

Dosing and schedule

Indications and contraindications

Precautions

Storage and logistics

Clinical studies - general characteristics

Vaccine efficacy and effectiveness

Efficacy of preclinical studies on the vaccine

Efficacy of the vaccine in clinical trials

Main immunogenicity outcomes

Main efficacy outcomes of the Bharat Biotech COVID-19 vaccine

Key messages

Contracting COVID-19 (measured at least 14 days after the second injection)

Contracting severe COVID-19 (measured at least 14 days after the second injection)

Efficacy of the vaccine in subgroups

Contracting COVID-19 (>60y) (measured at least 14 days after the second injection)

Summary of findings (iSoF)

Efficacy and effectiveness of the vaccine in subgroups

Vaccine effectiveness (other comparative studies)

Efficacy and effectiveness against SARS-CoV-2 variants

Vaccine efficacy and effectiveness for booster dose

Vaccine efficacy and effectiveness for heterologous schedule

Vaccine efficacy and effectiveness for heterologous booster schedule

Safety of the vaccine

Safety of the vaccine in preclinical studies

Safety of the vaccine in clinical trials

Local adverse events after the 1st dose (measured at least 7 days after vaccination)

Local adverse events after the 2nd dose (measured at least 7 days after vaccination)

Systemic adverse events after the 1st dose (measured at least 7 days after vaccination)

Systemic adverse events after the 2nd dose (measured at least 7 days after vaccination)

Any adverse event (median follow up 146 days)

Serious adverse events (median follow up 146 days)

Summary of findings (iSoF)

Safety of the vaccine in subgroups

Safety of the vaccine post-authorization

Monitoring

References

Contracting COVID-19 (measured at least 14 days after the second injection)

Contracting severe COVID-19 (measured at least 14 days after the second injection)

Contracting COVID-19 (>60y) (measured at least 14 days after the second injection)