Bharat Biotech COVID-19 vaccine

Extended version of the vaccine

Bharat Biotech COVID-19 vaccine

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: Authorized for emergency use in 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

Dose-finding studies

The BBIL/BBV152-A/2020 trial assessed 380 healthy participants aged 12 to 65 years that received two vaccination schedules, 3 μg with Algel-IMDG or 6 μg with Algel-IMDG. Vaccines were administered intramuscularly at a volume of 0.5 mL per dose in a two-dose regimen on day 0 and day 28. Findings showed that seroconversion rates were 98.4% (95% CI 95.3 to 99.7) in the 3 µg with Algel-IMDG group and 96.6% (95% CI 92.8 to– 98.8) in the 6 µg with Algel-IMDG group, at day 56. Both doses of the vaccine-induced significant neutralizing antibody responses to live SARS-CoV-2 [Ella R, 2021 ].

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.

Precautions
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.

Persons living with HIV [WHO, 2022 ].
Data on the administration of the Bharat Biotech COVID-19 vaccine are currently insufficient to allow the assessment of efficacy for persons living with HIV.
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.

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






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 ].

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

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

Randomized trials 

BBIL/BBV152-A/2020 was a phase 1/2 randomized trial (registered with the number NCT04471519 [Bharat Biotech International Limited, 2020 ]), sponsored by Bharat Biotech International Limited that was conducted in India. In the phase 1 trial, the aim was to evaluate the safety, reactogenicity, tolerability, and immunogenicity the vaccine. It was first registered in July 2020 and enrolled 375 participants of 18 to 55 years of age that were randomized in a 4:1 ratio to receive either one of three vaccine formulations or a control vaccine. Results were published in a scientific journal on January 2021 [Ella R, 2021 ].

The phase 2 of the trial [Ella R, 2021 ] randomized 380 participants of 12 to 65 years of age in a 1:1 ratio to receive one of two vaccine schedules. The interim results of the trial were published in a scientific journal on March, 2021 [Ella R, 2021 ].

A phase 2, double-blind, randomized controlled report was published of BBIL/BBV152-A/2020 trial (registered with the number NCT04471519 [Bharat Biotech International Limited, 2020 ]) sponsored by Bharat Biotech International Limited and conducted in India [Ella R, 2021 ]. It was first registered in July 2020 and enrolled 184 healthy volunteers ≥ 12 to 64 years of age that received a third (booster) dose of vaccine or placebo in a 1:1 ratio. The intervention was administered as a whole-virion ß-propiolactone-inactivated SARSCoV-2 vaccine adjuvanted with Algel-IMDG or a placebo containing sterile phosphate-buffered saline and Algel The study ended in June 2021.

Ella R et al. also known as BBIL/BBV152-C/2020 or CTRI/2020/11/028976, was a randomized phase 3 trial (registered with the numbers NCT04641481 [Bharat Biotech International Limited, 2020 ]) sponsored by Bharat Biotech International Limited that is being conducted in India. It was first registered in November 2020 and enrolled 25800 adults of 18 years of age or older, that received two intramuscular 6 µg Algel-IMDG doses of BBV152 or placebo on days 0 and 28. It is expected to run until December 2022. Data was published in a peer-reviewed journal in December 2021 [Ella R, 2021 ].

 


Other studies providing efficacy or safety data

The following non-comparative studies have reported efficacy or safety data:

Srivastava et al. [Srivastava RK, 2021 ];

Singh et al. [AWADHESH KUMAR SINGH, 2021 ];

Parai et al. [Parai D, 2021 ];

Tyagi et al. [Tyagi K, 2021 ];

Arora et al. [Arora P, 2021 ];

Khawaja et al. [Khawaja T, 2021 ].

Methods used to assess efficacy

In the Ella R et al. (phase 3) [Raches Ella MBBS, MS, 2021 ], the primary endpoint was specified in preventing a first occurrence of symptomatic COVID-19 (any severity) with onset at least 14 days after the second dose among participants who were SARS-CoV-2 negative by PCR and serology at baseline, had no major protocol deviations, and followed-up for at least two weeks after the second dose. End points were judged by an independent adjudication committee that was unaware of group assignment.

COVID-19 cases were defined as participants with at least two of the following symptoms: fever (temperature ≥ 38°C), chills, myalgia, headache, sore throat, or new olfactory or taste disorder, or had at least one respiratory sign or symptom (including cough, shortness of breath, or clinical or radiographic evidence of pneumonia) and at least one SARS-CoV-2 PCR-positive nasopharyngeal swab. COVID-19 cases were followed daily to assess symptom severity until symptoms resolved. In PCR-positive participants who consented, an additional NP swab for genotyping and a blood sample for evaluating correlates of protection were collected [Raches Ella MBBS, MS, 2021 ].

Safety evaluation methods

Safety assessments included: Medically Attended Adverse Events, Adverse Events of Special Interest, Solicited Local and Systemic Adverse Reactions, Unsolicited Adverse Events, Immediate Adverse events, and Serious Adverse Events

End points were judged by an independent adjudication committee that was unaware of group assignment.

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 Bharat Biotech COVID-19 vaccine

Key messages

There is no evidence available at this moment to assess the efficacy of Bharat Biotech COVID-19 vaccine.

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 high.


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.

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


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).

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)


Efficacy and effectiveness of the vaccine in subgroups

Sex

Randomized trials

There are no phase 3 randomized trials that have yet reported outcome data. The differential efficacy 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 Ella R, et al. phase 3 randomized trial, 1,858 participants were enrolled: 893 received the Bharat Biotech COVID-19 vaccine and 965 were assigned the placebo. The efficacy was assessed 14 days after the second injection. For participants over the age of 60 years old, the efficacy against symptomatic COVID-19 was 67.8% (95% CI: 8 to 90). [Ella R, 2021 ]

 

Children and adolescents

Randomized trials

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

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

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

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

Main effectiveness outcomes of Bharat Biotech COVID-19 vaccine (Other 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 vaccine effectiveness of 44% (95% CI 37 to 51) against symptomatic infection, hospitalization or death and 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 ]

 

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 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 vaccine effectiveness of 44% (95% CI 37 to 51) against symptomatic infection, hospitalization or death and vaccine effectiveness of 61% (95% CI 37 to 76) against hospitalization or death [Sumit Malhotra, 2022 ].

 

Transmission

No studies reported or assessed this outcome

SARS-CoV-2 variants

Immunogenicity outcomes

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 neutralization 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 ].

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 the Beta variant GMT: 187.5 (95%CI 129.3 to 271.9) [Yadav PD, 2021 ].

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 Delta variant GMT 61.57 (95% CI 36.3 to104.3) [Yadav PD, 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 ].

 BBIL/BBV152-A/2020 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 ].

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 ].

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 ]. 

 

Randomized trials

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) [Raches Ella MBBS, MS, 2021 ].

Other studies

To date, no studies have assessed the vaccine efficacy outcomes against SARS-CoV-2 variants.

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 d post-immunization. The results showed that Results show the persistence of T cell responses up to 6 months after the second dose. Vaccine-induced SARS-CoV-2 recall responses were demonstrated by the presence of SARS-CoV-2-specific CD4+ or CD8+ central, effector, and terminally differentiated effector memory cells that re-express CD45RA T cell population. In addition, higher levels of neutralizing antibodies were observed with both assays than those observed after the two doses primary series[Krishna Mohan Vadrevu, 2022 ].

BBIL/BBV152-A/2020 included 13 booster vaccine recipients. Data were collected 28 days after booster dose. The study showed that 100% and 90% of subjects showed neutralizing activity against the Delta and Omicron variants respectively. This  was however lower compared to neutralization against the vaccine strain [Venkata V Edara, 2022 ].

Heterologous vaccine regimens

Immunogenicity outcomes

To date, no studies have assessed the vaccine immunogenicity outcomes on heterologous regimen.

 

Heterologous-booster regimens

Immunogenicity outcomes

To date, no studies have assessed the vaccine immunogenicity outcomes on a heterologous-booster regimen.

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

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

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

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

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

There are no phase 3 randomized trials that have yet reported outcome data. 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 diference 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 ].

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 ].

 

Monitoring

WHO recommends the following research and post-authorization monitoring activities:

Safety surveillance and monitoring
- Serious adverse events, anaphylaxis and other serious allergic reactions, Bell’s palsy, cases of multisystem inflammatory syndrome following vaccination, cases of COVID-19 following vaccination that result in hospitalization or death.

Vaccine effectiveness
− Vaccine effectiveness over time and whether protection can be prolonged by booster doses.
− Studies to investigate whether this vaccine reduces SARS-CoV-2 transmission and viral shedding.
− Assessment and reporting of vaccination failures and virus sequence information.

Subgroups
− Prospective studies on the safety of COVID-19 vaccine in pregnant and lactating females.
− Randomized controlled trials on efficacy and safety of vaccination in children below the age of 18 years.
− Safety data on vaccination in immunocompromised people, including patients living with HIV and autoimmune disease.

Vaccination logistics
− Immunogenicity and safety studies of co-administration with other vaccines, including influenza and pneumococcal vaccines, to adults and older persons.
− Safety, immunogenicity, and impact of a delayed second dose, as currently implemented by certain countries.
− Stability of the vaccine under alternative cold-chain distribution and storage conditions.
− Effectiveness of the proposed strategies for the prevention and management of anaphylactic reactions.
− Interchangeability studies within and across COVID-19 vaccine platforms.

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;
[WHO, 2022] WHO. Suspension of supply of COVID-19 vaccine (COVAXIN®). 2022; WHO. Suspension of supply of COVID-19 vaccine (COVAXIN®). 2022;
[WHO, 2022] WHO. Interim recommendations for use of the Bharat Biotech BBV152 COVAXIN® vaccine against COVID-19. 2022; WHO. Interim recommendations for use of the Bharat Biotech BBV152 COVAXIN® vaccine against COVID-19. 2022;
[Ministry of Health and Family Welfare. Government of India, 2021] Ministry of Health and Family Welfare. Government of India. Press Statement by the Drugs Controller General of India (DCGI) on Restricted Emergency approval of COVID-19 virus vaccine. Press release - HFW/DCGI Media statement on COVID Vaccine/3rd January20 Ministry of Health and Family Welfare. Government of India. Press Statement by the Drugs Controller General of India (DCGI) on Restricted Emergency approval of COVID-19 virus vaccine. Press release - HFW/DCGI Media statement on COVID Vaccine/3rd January20
[COFREPRIS, 2021] COFREPRIS. COFEPRIS ISSUES AUTHORIZATION FOR EMERGENCY USE OF VACCINE AGAINST COVID-19 COVAXIN. C. Pb. No. 09 /2021 - 5 March 2021. 2021; COFREPRIS. COFEPRIS ISSUES AUTHORIZATION FOR EMERGENCY USE OF VACCINE AGAINST COVID-19 COVAXIN. C. Pb. No. 09 /2021 - 5 March 2021. 2021;
[Ganneru B, 2021] Ganneru B, Jogdand H, Daram VK et al. Th1 Skewed immune response of Whole Virion Inactivated SARS CoV 2 Vaccine and its safety evaluation. iScience. 2021;:102298. Ganneru B, Jogdand H, Daram VK et al. Th1 Skewed immune response of Whole Virion Inactivated SARS CoV 2 Vaccine and its safety evaluation. iScience. 2021;:102298.
[Gao Q, 2020] Gao Q, Bao L, Mao H et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science (New York, N.Y.). 2020;369(6499):77-81. Gao Q, Bao L, Mao H et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science (New York, N.Y.). 2020;369(6499):77-81.
[Tseng CT, 2012] Tseng CT, Sbrana E, Iwata-Yoshikawa N et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PloS one. 2012;7(4):e35421. Tseng CT, Sbrana E, Iwata-Yoshikawa N et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PloS one. 2012;7(4):e35421.
[Qiang Gao, 2020] Qiang Gao, Linlin Bao, Haiyan Mao et al. Rapid development of an inactivated vaccine for SARS-CoV-2. bioRxiv. 2020; Qiang Gao, Linlin Bao, Haiyan Mao et al. Rapid development of an inactivated vaccine for SARS-CoV-2. bioRxiv. 2020;
[Ella R, 2021] Ella R, Reddy S, Jogdand H et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. The L Ella R, Reddy S, Jogdand H et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. The L
[WHO, 2021] WHO. COVID-19 vaccination: supply and logistics guidance: interim guidance, 12 February 2021. WHO/2019-nCoV/vaccine_deployment/logistics/2021.1. 2021; WHO. COVID-19 vaccination: supply and logistics guidance: interim guidance, 12 February 2021. WHO/2019-nCoV/vaccine_deployment/logistics/2021.1. 2021;
[Bharat Biotech International Limited, 2020] Bharat Biotech International Limited. Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152) for COVID-19 in Healthy Volunteers. clinicaltrials.gov. 2020; Bharat Biotech International Limited. Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152) for COVID-19 in Healthy Volunteers. clinicaltrials.gov. 2020;
[Ella R, 2021] Ella R, Vadrevu KM, Jogdand H et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. The Lancet. Infectious diseases. 2021;21(5):637-646. Ella R, Vadrevu KM, Jogdand H et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. The Lancet. Infectious diseases. 2021;21(5):637-646.
[Bharat Biotech International Limited, 2020] Bharat Biotech International Limited. A Phase 3 Efficacy and Safety Clinical Trial of a Whole Virion Inactivated SARS-CoV-2 Vaccine (BBV152). clinicaltrials.gov. 2020; Bharat Biotech International Limited. A Phase 3 Efficacy and Safety Clinical Trial of a Whole Virion Inactivated SARS-CoV-2 Vaccine (BBV152). clinicaltrials.gov. 2020;
[Ella R, 2021] Ella R, Reddy S, Blackwelder W et al. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. Lancet (London, England). 2021; Ella R, Reddy S, Blackwelder W et al. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. Lancet (London, England). 2021;
[Srivastava RK, 2021] Srivastava RK, Ish P, Covid-Vaccination Group S. The initial experience of COVID-19 vaccination from a tertiary care centre of India. Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace. 2021; Srivastava RK, Ish P, Covid-Vaccination Group S. The initial experience of COVID-19 vaccination from a tertiary care centre of India. Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace. 2021;
[AWADHESH KUMAR SINGH, 2021] AWADHESH KUMAR SINGH, Sanjeev Phatak, Nagendra Kumar Singh et al. Antibody Response after First-dose of ChAdOx1-nCOV (Covishield) and BBV-152 (Covaxin) amongst Health Care Workers in India: Preliminary Results of Cross-sectional Coronavirus Vaccine-induce AWADHESH KUMAR SINGH, Sanjeev Phatak, Nagendra Kumar Singh et al. Antibody Response after First-dose of ChAdOx1-nCOV (Covishield) and BBV-152 (Covaxin) amongst Health Care Workers in India: Preliminary Results of Cross-sectional Coronavirus Vaccine-induce
[Parai D, 2021] Parai D, Choudhary H, Dash G et al. Effect of a single-dose of BBV-152 and AZD1222 on Spike antibody titre among healthcare workers previously infected with SARS-CoV-2. ResearchSquare. 2021; Parai D, Choudhary H, Dash G et al. Effect of a single-dose of BBV-152 and AZD1222 on Spike antibody titre among healthcare workers previously infected with SARS-CoV-2. ResearchSquare. 2021;
[Tyagi K, 2021] Tyagi K, Ghosh A, Nair D et al. Breakthrough COVID19 infections after vaccinations in healthcare and other workers in a chronic care medical facility in New Delhi, India. Diabetes & metabolic syndrome. 2021;15(3):1007-1008. Tyagi K, Ghosh A, Nair D et al. Breakthrough COVID19 infections after vaccinations in healthcare and other workers in a chronic care medical facility in New Delhi, India. Diabetes & metabolic syndrome. 2021;15(3):1007-1008.
[Arora P, 2021] Arora P, Sardana K, Mathachan SR et al. Herpes zoster after inactivated COVID-19 vaccine: a cutaneous adverse effect of the vaccine. Journal of cosmetic dermatology. 2021; Arora P, Sardana K, Mathachan SR et al. Herpes zoster after inactivated COVID-19 vaccine: a cutaneous adverse effect of the vaccine. Journal of cosmetic dermatology. 2021;
[Khawaja T, 2021] Khawaja T, Jaswaney R, Arora N et al. The Impact of SARS-COV-2 Variants on Vaccine Efficacy Amongst Healthcare Workers During India’s Second Wave. ResearchSquare. 2021; Khawaja T, Jaswaney R, Arora N et al. The Impact of SARS-COV-2 Variants on Vaccine Efficacy Amongst Healthcare Workers During India’s Second Wave. ResearchSquare. 2021;
[Raches Ella MBBS, MS, 2021] Raches Ella MBBS, MS, Siddharth Reddy MSc, William Blackwelder PhD et al. Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a double-blind, randomised, controlled phase 3 trial. medRxiv. 2021; Raches Ella MBBS, MS, Siddharth Reddy MSc, William Blackwelder PhD et al. Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a double-blind, randomised, controlled phase 3 trial. medRxiv. 2021;
[Mohandas S, 2021] Mohandas S, Yadav PD, Shete-Aich A et al. Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS- CoV-2 vaccine candidates in the Syrian hamster model. iScience. 2021;24(2):102054. Mohandas S, Yadav PD, Shete-Aich A et al. Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS- CoV-2 vaccine candidates in the Syrian hamster model. iScience. 2021;24(2):102054.
[Yadav PD, 2021] Yadav PD, Ella R, Kumar S et al. Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques. Nature communications. 2021;12(1):1386. Yadav PD, Ella R, Kumar S et al. Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques. Nature communications. 2021;12(1):1386.
[The GRADE Working Group, 2013] The GRADE Working Group. GRADE handbook for grading quality of evidence and strength of recommendations. Schünemann H, Bro?ek J, Guyatt G, Oxman A, editors. 2013; The GRADE Working Group. GRADE handbook for grading quality of evidence and strength of recommendations. Schünemann H, Bro?ek J, Guyatt G, Oxman A, editors. 2013;
[Sumit Malhotra, 2022] Sumit Malhotra, Kalaivani Mani, Rakesh Lodha et al. Effectiveness of BBV152 vaccine against SARS-CoV-2 infections, hospitalizations, and deaths among healthcare workers in the setting of high delta variant transmission in New Delhi, India. medRxiv. 2022; Sumit Malhotra, Kalaivani Mani, Rakesh Lodha et al. Effectiveness of BBV152 vaccine against SARS-CoV-2 infections, hospitalizations, and deaths among healthcare workers in the setting of high delta variant transmission in New Delhi, India. medRxiv. 2022;
[Malhotra S, 2022] Malhotra S, Mani K, Lodha R et al. SARS-CoV-2 Reinfection Rate and Estimated Effectiveness of the Inactivated Whole Virion Vaccine BBV152 Against Reinfection Among Health Care Workers in New Delhi, India. JAMA network open. 2022;5(1):e2142210. Malhotra S, Mani K, Lodha R et al. SARS-CoV-2 Reinfection Rate and Estimated Effectiveness of the Inactivated Whole Virion Vaccine BBV152 Against Reinfection Among Health Care Workers in New Delhi, India. JAMA network open. 2022;5(1):e2142210.
[Sapkal GN, 2021] Sapkal GN, Yadav PD, Ella R et al. Inactivated COVID-19 vaccine BBV152/COVAXIN effectively neutralizes recently emerged B 1.1.7 variant of SARS-CoV-2. Journal of travel medicine. 2021; Sapkal GN, Yadav PD, Ella R et al. Inactivated COVID-19 vaccine BBV152/COVAXIN effectively neutralizes recently emerged B 1.1.7 variant of SARS-CoV-2. Journal of travel medicine. 2021;
[Yadav PD, 2021] Yadav PD, Sapkal GN, Ella R et al. Neutralization of Beta and Delta variant with sera of COVID-19 recovered cases and vaccinees of inactivated COVID-19 vaccine BBV152/Covaxin. Journal of travel medicine. 2021; Yadav PD, Sapkal GN, Ella R et al. Neutralization of Beta and Delta variant with sera of COVID-19 recovered cases and vaccinees of inactivated COVID-19 vaccine BBV152/Covaxin. Journal of travel medicine. 2021;
[Pragya D Yadav, 2021] Pragya D Yadav, Rima R Sahay, Gajanan Sapkal et al. Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152. bioRxiv. 2021; Pragya D Yadav, Rima R Sahay, Gajanan Sapkal et al. Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152. bioRxiv. 2021;
[Krishna Mohan Vadrevu, 2022] Krishna Mohan Vadrevu, Brunda Ganneru, Siddharth Reddy et al. Persistence of immunity and impact of a third (booster) dose of an inactivated SARS-CoV-2 vaccine, BBV152; a phase 2, double-blind, randomised controlled trial. medRxiv. 2022; Krishna Mohan Vadrevu, Brunda Ganneru, Siddharth Reddy et al. Persistence of immunity and impact of a third (booster) dose of an inactivated SARS-CoV-2 vaccine, BBV152; a phase 2, double-blind, randomised controlled trial. medRxiv. 2022;
[Venkata V Edara, 2022] Venkata V Edara, Mit Patel, Mehul S Suthar. Covaxin (BBV152) Vaccine Neutralizes SARS-CoV-2 Delta and Omicron variants. medRxiv. 2022; Venkata V Edara, Mit Patel, Mehul S Suthar. Covaxin (BBV152) Vaccine Neutralizes SARS-CoV-2 Delta and Omicron variants. medRxiv. 2022;
[Das, S., 2022] Das, S., Singh, J., Shaman, H. et al. Antibody response after a single dose of BBV152 vaccine negatively correlates with pre-existing antibodies and induces a significant but low levels of neutralizing antibodies to Omicron variant. medRxiv. 2022; Das, S., Singh, J., Shaman, H. et al. Antibody response after a single dose of BBV152 vaccine negatively correlates with pre-existing antibodies and induces a significant but low levels of neutralizing antibodies to Omicron variant. medRxiv. 2022;
[Joshi PC, 2021] Joshi PC, Jahanvi V, Mahajan MS et al. Getting Vaccinated Helps: Prospective Study Reveals Lower CT Severity Scores amongst COVID Vaccine Recipients. The Indian journal of radiology & imaging. 2021;31(4):888-892. Joshi PC, Jahanvi V, Mahajan MS et al. Getting Vaccinated Helps: Prospective Study Reveals Lower CT Severity Scores amongst COVID Vaccine Recipients. The Indian journal of radiology & imaging. 2021;31(4):888-892.
[Cherian S, 2021] Cherian S, Paul A, Ahmed S et al. Safety of the ChAdOx1 nCoV-19 and the BBV152 vaccines in 724 patients with rheumatic diseases: a post-vaccination cross-sectional survey. Rheumatology international. 2021; Cherian S, Paul A, Ahmed S et al. Safety of the ChAdOx1 nCoV-19 and the BBV152 vaccines in 724 patients with rheumatic diseases: a post-vaccination cross-sectional survey. Rheumatology international. 2021;
[Parida SP, 2022] Parida SP, Sahu DP, Singh AK et al. Adverse Events Following Immunization of COVID-19 (Covaxin) vaccine at a Tertiary Care Center of India. Journal of medical virology. 2022; Parida SP, Sahu DP, Singh AK et al. Adverse Events Following Immunization of COVID-19 (Covaxin) vaccine at a Tertiary Care Center of India. Journal of medical virology. 2022;
[Nasergivehchi S, 2022] Nasergivehchi S, Togha M, Jafari E et al. Headache Following COVID-19 Vaccination Among Healthcare Employees With a History of COVID-19 Infection: a Cross-sectional Study in Iran With a Meta-analytic Review of the Literature. ResearchSquare. 2022; Nasergivehchi S, Togha M, Jafari E et al. Headache Following COVID-19 Vaccination Among Healthcare Employees With a History of COVID-19 Infection: a Cross-sectional Study in Iran With a Meta-analytic Review of the Literature. ResearchSquare. 2022;
[Houshmand B, 2022] Houshmand B, Keyhan SO, Fallahi HR et al. Vaccine-associated complications: a comparative multicenter evaluation among dental practitioners and dental students-which candidate vaccine is more safe in SARS COV II, Gam-COVID-Vac (Sputnik V), ChAdOx1 nCoV-19 Houshmand B, Keyhan SO, Fallahi HR et al. Vaccine-associated complications: a comparative multicenter evaluation among dental practitioners and dental students-which candidate vaccine is more safe in SARS COV II, Gam-COVID-Vac (Sputnik V), ChAdOx1 nCoV-19
Back to dashboard