Anhui Zhifei Longcom COVID-19 vaccine

Extended version of the vaccine

Alternative names:
Zifivax; ZF-UZ-VAC 2001; ZF2001

Authorization

World Health Organization Emergency Use Listing Procedure

Not authorized.
Expression of interest under assessment [Last checked at WHO EUL official website on January 12th 2023].

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

China's National Medical Products Administration
Authorized on 17 March 2021 [China's National Medical Products Administration, 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)
Not authorized.

Health Canada
Not authorized.

Public Health Institute (ISP, Chile)
Not authorized.

National Institute of Food and Drug Monitoring (INVIMA, Colombia)
Authorized for emergency use on 12 January 2022 [INVIMA, 2022 ].

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)
Not authorized.

Authorization in jurisdictions in Latin America and the Caribbean
Not authorized.

Authorization in other jurisdictions
Indonesia
Uzbekistan

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

Manufacturing

Manufacturer
Anhui Zhifei Longcom Biopharmaceutical Co.Ltd., China. Sponsor of the vaccine clinical trials and main manufacturer [Business Insider, 2021 ].

Other manufacturers
Not described.

General characteristics

The Anhui Zhifei Longcom COVID-19 vaccine is an adjuvanted protein subunit COVID-19 vaccine. The protein subunit vaccine targets the receptor-binding domain (RBD) for SARS-CoV-2 located at C-terminal domain of S1 subunit in S protein (between R319 to K537) [An Y, 2021 ].

The protein was engineered as a tandem-repeat dimeric RBD to increase immunogenicity. Compared to the traditional monomeric RBD, RBD-dimer enhances the SARS-CoV-2 neutralizing antibodies [Dai L, 2020 ].

RBD is considered an attractive coronavirus vaccine target, because it focuses in the antibody response to block the receptor binding, therefore, poses low potential for antibody-dependent enhancement risk [Dai L, 2020 ].

The construct of RBD-dimer is produced in clinical-grade Chinese hamster ovary (CHO) cell lines and then formulated with aluminum hydroxide as an adjuvant, resulting in the final vaccine product [An Y, 2021 ].

Ingredients

Active ingredient
Recombinant SARS-CoV-2 RBD protein 25 μg

Excipients
Aluminum hydroxide adjuvant 0.25 mg
Sodium chloride
Disodium phosphate
L-Histidine

Risk considerations

Peptide-based vaccines have theoretical advantages over traditional whole-organism and other platforms. They allow the immune response to focus on the protective epitopes and to exclude non-relevant epitopes, including those reactogenic or allergenic, at the stage of vaccine design [Reche PA, 2014 ].

Dosing and schedule

Anhui Zhifei Longcom COVID-19 vaccine is administered as a series of three doses (0.5 mL each) 4 and 8 weeks apart.

The pharmaceutical form is a suspension for intramuscular injection.
The preferred site of injection is the deltoid muscle of the upper arm.

If the administration of the second or third dose is inadvertently delayed it should be given as soon as possible, according to the manufacturer’s instructions.

Booster dose
Current recommendations do not suggest that individuals receive more than three doses of the Anhui Zhifei Longcom COVID-19 vaccine.

Heterologous COVID-19 vaccine schedules
Individuals starting a series with the Anhui Zhifei Longcom COVID-19 vaccine must complete the series with the same product.
There is no available data to support the interchangeability between the Anhui Zhifei Longcom COVID-19 vaccine and other vaccines against COVID-19.

Vaccination schedule for immunocompromised persons [INVIMA, 2022 ]
INVIMA (Colombia) recommends a primary series of three doses (0.5 mL each) provided 4 and 8 weeks apart.

Indications and contraindications

Indications

Anhui Zhifei Longcom COVID-19 vaccine is indicated for individuals 18 years of age and older [NMPA, 2021 ].

Contraindications

The vaccine is contraindicated in individuals with a known history of a severe allergic reaction to any component of the vaccine (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 Anhui Zhifei Longcom COVID-19 vaccine.

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

Precautions

Allergic reactions
Persons with a history of anaphylaxis to any other vaccine or injectable therapy should be observed in health care settings where anaphylaxis can be immediately treated.

Pregnancy and breastfeeding
The available data on Anhui Zhifei Longcom COVID-19 vaccine is insufficient to assess vaccine efficacy in pregnancy and breastfeeding since no clinical trials have included pregnant or breastfeeding women [INVIMA, 2022 ].

Children and adolescents [NMPA, 2021 ]
There are limited data on the efficacy or safety of persons below 18 years of age for this vaccine. Until more data are available, vaccination of individuals in this age range is not routinely recommended.

Older persons [NMPA, 2021 ].
Vaccination is recommended for older persons without an upper age limit

Persons with previous SARS-CoV-2 infection
Vaccination may be offered regardless of a person’s history of symptomatic or asymptomatic SARS-CoV-2 infection.

Persons with current acute COVID-19
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 [PAHO, 2020 ].

Other precautions
As with other intramuscular injections, the vaccine should be given with caution in individuals with bleeding disorders or other conditions that increase the risk of bleeding, such as anticoagulant therapy, thrombocytopenia and hemophilia.
WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination.
Administer with precaution in persons with epilepsy or progressive neurological disorders [INVIMA, 2022 ].

Co-administration with other vaccines
There should be a minimum interval of 14 days between the administration of this vaccine with any other vaccine in the immunization schedule, until data on co-administration with other vaccines are available.

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.

Storage and logistics

Storage

Anhui Zhifei Longcom COVID-19 vaccine is provided as a suspension stored at 5°C/41°F (between 2°C to 8°C [35°F to 46°F])[Yang S, 2021 ].

Protect the vials from light.
Do not freeze.

Administration logistics

Inspect the vial before use.
The vial should be discarded if particles or differences are observed in the described appearance of the vaccine.
Shake the vial gently.

Storage after first puncture

After the first puncture of the vial, preferably use immediately.
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
NCV-Ⅰ-healthy is a phase 1 randomized trial (registered with the number NCT04466085 [Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2020 ]) sponsored by Anhui Zhifei Longcom Biopharmaceutical that is being conducted in China [Yang S, 2021 ]. It was first registered in June 2020 and has enrolled 50 healthy adults aged 18–59 years that received three doses of the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart in a 2:2:1 ratio. It is expected to run until September 2021. The first report of outcome data published in a scientific journal was released in March 2021.

NCV-Ⅱ-healthy is a phase 2 randomized trial (registered with the number NCT04466085 [Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2020 ]) sponsored by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. that is being conducted in China [Yang S, 2021 ]. It was first registered in July 2020 and has enrolled 900 healthy people aged 18 to 59 years that received the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule in a 1:1:1:1:1:1 ratio. It is expected to run until December 2021. The first report of outcome data published in a scientific journal was released in March 2021.

LKM-2020-NCV-GJ01 was a phase-3 randomized trial (registered with the number NCT04646590) sponsored by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. It included 28,873 adult participants (≥18 years of age) from 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador between 12 December 2020, and 15 December 2021. An additional center in China was included for the safety analysis. Participants were randomized to receive three injections of ZF2001 or placebo 30 days apart [Dai L, 2022 ].

Other studies providing efficacy or safety data
LKM-2021-NCV-JQ01 is an ongoing phase 1/2 non-randomized study (registered with the number NCT05198063) sponsored by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. [Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2022 ]. It was first registered in January 2022 and plans to enroll 300 adults 18 years old and over who have completed the primary vaccination series of Anhui Zhifei Longcom COVID-19 vaccine.Those participants will receive a booster dose of the vaccine 6 months after the primary vaccination series. It is expected to run for until July 2022.
LKM-2021-NCV-JQ02 is an ongoing phase 1/2 non-randomized study (registered with the number NCT05198102) sponsored by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.[Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2021 ]. It was first registered in January 2022 and plans to enroll 300 adults 18 years old and over who have completed the primary vaccination series of Anhui Zhifei Longcom COVID-19 vaccine. Those participants will receive a booster dose of the vaccine 12 months after the primary vaccination series. It is expected to run for until July 2022.
IIT-LKM-2021-NCV03-02 is an ongoing phase 1/2 non-randomized study (registered with the number NCT05205096 [Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2021 ]) sponsored by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. that is being conducted in China. It was first registered in January 2022 and plans to enroll 480 adults 18 years old and over who have completed the primary vaccination series of Sinovac COVID-19 vaccine. Those participants will receive a booster dose of Anhui Zhifei Longcom COVID-19 vaccine 3-9 months after the primary vaccination series. It is expected to run until June 2022.
IIT-LKM-2021-NCV03-01 is an ongoing phase 1/2 non-randomized study (registered with the number NCT05205083 [Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2021 ]) sponsored by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. that is being conducted in China. It was first registered in January 2022 and plans to enroll 480 adults 18 years old and over who have completed the primary vaccination series of Sinopharm/BIBP COVID-19 vaccine. Those participants will receive a booster dose of Anhui Zhifei Longcom COVID-19 vaccine 3-9 months after the primary vaccination series. It is expected to run until July 2022.

Vaccine efficacy and effectiveness

Efficacy of preclinical studies on the vaccine

The immunogenicity of the vaccine was evaluated in mice and nonhuman primates [An Y, 2021 ].

To study the immunogenicity, groups of BALB/c mice were vaccinated with two doses of 10 µg of the vaccine, 21 days apart. Mice receiving placebo (adjuvant only) were used as negative control. Serum samples from mice were collected at different time points after vaccination to monitor the duration of antibody responses. The geometric mean titer was 256 on day 35, after the second dose, the mean titers remained high until the last sample was taken at 140 days, suggesting that the humoral responses induced by the vaccine would be durable in time [An Y, 2021 ].

Young rhesus macaques were immunized with two doses of 25 μg or 50 μg vaccine intramuscularly, 21 days apart. Macaques that received a placebo were used as controls. The results showed that both doses elicited high levels of serological RBD-binding IgG and SARS-CoV-2 neutralizing antibodies after one or two immunizations [An Y, 2021 ].

Efficacy of the vaccine in clinical trials

Main immunogenicity outcomes

Combined analysis of NCV-Ⅱ-healthy and NCV-Ⅰ-healthyphase 1/2 trials. Phase 1 trial enrolled 50 participants that were assigned to receive three doses of placebo (n=10), the 25 µg vaccine (n=20), or the 50 µg vaccine (n=20). The mean age of participants was 32.6 years. Phase 2 trial enrolled 900 participants that were assigned to receive different schemes of vaccination. One group of participants was assigned to receive two doses of placebo (n=150), 25 µg vaccine (n=150), or 50 µg vaccine (n=150). While, the second group was assigned to receive three doses of placebo (n=150), 25 µg vaccine (n=150), or 50 µg vaccine (n=150). The mean age of participants was 43.5 years [Yang S, 2021 ].

In the phase 1 trial, the main immunogenicity outcome was measured with the serological RBD-binding IgG titres with ELISA test to assess antibody responses. Results showed that seroconversion rates, at day 30 after the second dose, reached 93% (14 of 15 participants) in the 25 µg group and 94% (17 of 18 participants) in the 50 µg group. The SARS-CoV-2-neutralising GMTs were 14% (95% CI 8-24.6) in the 25 µg group and 11.4% (95% CI 6.6-19.8) in the 50 µg group at day 30 after the second dose, and increased to 94.5% (95% CI 49.3-181.3) in the 25 µg group and 117.8% (95% CI 64.6-214.9) in the 50 µg group at day 7 after the third dose [Yang S, 2021 ].

In the two-dose groups in phase 2 of the trial, on day 14 after the third dose, seroconversion rates were 0% (none of 140) in the placebo group, 99% (143 of 144) in the 25 µg group and 97% (139 of 143) in the 50 µg group. The neutralizing GMTs for SARS-CoV-2, 14 days after the second dose were 17.7% (95% CI: 13.6-23) in the 25 µg group and 14% (95% CI : 10.8-18.3) in the 50 µg group. While in the group that received all three doses, the neutralizing GMTs of SARS-CoV-2 14 days later were 102.5% (95% CI: 81.8-128.5) in the group of 25 µg and 69% (95% CI 53-90) in the 50 µg group [Yang S, 2021 ].

Key messages

Anhui Zhifei Longcom COVID-19 vaccine reduces the risk of contracting COVID-19

Anhui Zhifei Longcom COVID-19 vaccine reduces the risk of contracting severe COVID-19

Main efficacy outcomes of Anhui Zhifei Longcom COVID-19 vaccine

Contracting COVID-19 (measured at least 14 days after the third dose)

The relative risk of Contracting COVID-19 in the group that received control vaccine, versus the group that received Anhui Zhifei Longcom COVID-19 vaccine was 0.27 (95% CI 0.23 to 0.32). This means Anhui Zhifei Longcom COVID-19 vaccine reduced the risk of contracting COVID-19 by 73%, compared with control vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19. Comparison: Anhui Zhifei Longcom COVID-19 vaccine versus control vaccine

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

Contracting severe COVID-19 (measured at least 14 days after the third dose)

The relative risk of contracting severe COVID-19 in the group that received control vaccine, versus the group that received Anhui Zhifei Longcom COVID-19 vaccine was 0.14 (95% CI 0.06 to 0.33). This means Anhui Zhifei Longcom COVID-19 vaccine reduced the risk of contracting severe COVID-19 by 86%, compared with control vaccine.

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

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

Mortality

The existing evidence does not allow to assess the impact of Anhui Zhifei Longcom COVID‑19 vaccine on the risk of mortality. The information provided by randomized trials was not adequately powered to estimate a difference in this outcome. Deaths can occur in the intervention and control group for reasons unrelated to COVID-19 or the vaccine. Establishing that there is a reduction (or increase) in the risk of death attributable to COVID-19 would require trials with a higher statistical power.

Summary of findings table (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 LKM-2020-NCV-GJ01 phase 3 trial [Dai L, 2022 ].

Age
Randomized trials
LKM-2020-NCV-GJ01 was a randomized, double-blind, placebo controlled, phase 3 trial, which investigate the efficacy and safety of ZF2001. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-μg doses (30 days apart) of ZF2001 or placebo. A total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data. Vaccine efficacy against symptomatic COVID-19 infection was 67.6% (95% CI 21.9 to 87.8), RR 0,32 (CI 95% 0,12-0,78).
.[Dai L, 2022 ]

Children and adolescents
Randomized trials
Children and adolescents were excluded from the LKM-2020-NCV-GJ01 phase 3 trial [Dai L, 2022 ], therefore no data are available for this subgroup.

Pregnancy
Randomized trials
Pregnant women were excluded from the LKM-2020-NCV-GJ01 phase 3 trial [Dai L, 2022 ], therefore no data are available for this subgroup.

Breastfeeding
Randomized trials
Breastfeeding women were excluded from the LKM-2020-NCV-GJ01 phase 3 trial [Dai L, 2022 ], therefore no data are available for this subgroup.

Immunocompromised persons
Randomized trials
Breastfeeding women were excluded from the LKM-2020-NCV-GJ01 phase 3 trial [Dai L, 2022 ], therefore no data are available for this subgroup.

Vaccine effectiveness (other comparative studies)

Contracting COVID-19
No studies reported or assessed this outcome

Contracting severe COVID-19
No studies reported or assessed this outcome

Transmission
No studies reported or assessed this outcome

Efficacy and effectiveness against SARS-CoV-2 variants

Immunogenicity outcomes
Alpha (B.1.1.7)
Zhao X et al. carried out a non-comparative study (neutralizing capacity from recipients' sera) in China, which included 28 vaccine recipients. The study reported data from the participants' serum samples. The results showed that the neutralizing titer did not decline, but slightly increased (1.1 fold to WT, P > 0.05), against B.1.1.7-spike pseudovirus. [Xin Zhao, 2021 ].

Beta (B.1.351)
Huang B et al. conducted a comparative study (neutralizing capacity from recipients' sera) in China, which included 12 vaccine recipients. The study reported data from the participants' serum samples. The results showed that Beta variant does not escape the immunity induced by vaccine targeting S protein dimeric RBD (Anhui Zhifei Longcom). GMT decreased from 106.1 (95% CI 75.0 to 150.1) to 66.6 (95% CI 51.0 to 86.9) [Huang B, 2021 ].

Cao Y et al. conducted a comparative study (neutralizing capacity from recipients' sera) in China, which included 20 Anhui Zhifei Longcom vaccine volunteers. The study reported data from the participants' serum samples. Results demonstrated that individuals are capable of inducing highly diverse anti-RBD NAbs that react differently toward the B.1.351 variant. These enable Anhui Zhifei Longcom vaccinees to exhibit a two times higher tolerance to 501Y.V2 variants [Cao Y, 2021 ].

Delta (B.1.617.2)
Zhao X et al. carried out a non-comparative study (neutralizing capacity from recipients' sera) in China, which included 28 vaccine recipients. The study reported data from the participants' serum samples. The results showed that the variant with double mutations in RBD B.1.617.2 [Delta]-spike showed roughly equivalent sensitivity to ZF2001-elicited antisera as compared with pseudovirus expressing WTspike (-1.1 and -1.2 fold to WT, respectively; p > 0.05) [Xin Zhao, 2021 ].

Omicron (B.1.1.529)
Zhang Z et al. conducted a comparative study in China, which included 904 participants with two doses of CoronaVac, who received CanSino, Anhui Zhifei or CoronVac boosters. The results show that booster vaccination increased GMT of neutralizing antibodies 86 (95% CI: 59 to 127), 14 days after vaccination. [Zhe Zhang, 2022 ].

Zhong J et al was a comparative study conducted in China. The study included 150 participants with two doses of CoronaVac vaccine: 50 received a low-dose aerosolized Ad5-nCoV booster, 50 received a high-dose aerosolized Ad5- nCoV booster, 50 received homologous booster and 14 received the ZF2001 booster. This study assessed whether heterologous immunization with aerosol inhalation induces robust antibody immune response. Neutralizing antibodies (NAbs) against Omicron for participants with low dose aerosolized Ad5-nCoV booster was 115.8 (95% CI, 48.63–73.86), for participants with high-dose aerosolized Ad5- nCoV booster was 115.8 (95% CI, 88.57–151.3) and 4.32 (95% CI, 4.00–4.84) for participants who received homologous booster. The conventional virus neutralizing assay confirmed that Ad5-nCoV booster induced higher titer of neutralizing antibodies than ZF2001 booster (116.80 (95% CI, 84.51–161.5) vs 4.40 (95% CI, 4.00–4.83). [Zhong J, 2022 ]

Zhao X et al was a comparative study evaluating the immunogenic response in participants receiving ZF-2001. The study included 97 participants, 20 of them received each dose at 0-1-2 months, 9 participants at 0-1-3 months, 16 participants at 0-1-6 months, 20 received 2 doses of inactivated vaccine and a booster dose of ZF-2001, 16 participants received each dose of ZF-2001 at 0-1-3 months and the sera was obtained 4-7 months after the booster dose. The study assessed neutralizing antibody titers against the prototype virus and Omicron subvariants. The titers of neutralizing antibodies against BA.1 as GMT had a fold change to prototype of 14.1 (-18.5-fold) in the 0-1-2 group, 54.7 (-8.0-fold) in the 0-1-3 group, 438.3 (-5.8-fold) in the 0-1-6 group, 89.9 (-7.4-fold) in the heterologous booster group and 44.0 (-5.9-fold) in the 0-1-3 group at 4-7m. The titers of neutralizing antibodies against BA.4-5 variants as GMT had a fold change to prototype of 7.7 (-31.6-fold) in the 0-1-2 group, 24.5 (-23.4-fold) in the 0-1-3 group, 270 (-10.8-fold) in the 0-1-6 group, 30.8 (-19.4-fold) in the heterologous boost group, 16.7 (-12.6-fold) 0-1-3 group at 4-7 months. [Zhao X, 2022 ].

Vaccine efficacy and effectiveness for booster dose

Immunogenicity outcomes
JSVCT115 was a phase 4 randomized trial in China that included 120 participants who received a primary CanSino vaccine and one or two Anhui Zhifei Longcom boosters. Live virus-neutralizing antibody titers against WT SARS-CoV-2 isolate were measured 14 days after booster injection. A heterologous booster dose with ZF001 induced a significantly higher neutralizing antibody against the SARS-CoV-2 wild-type virus compared with the baseline (day 28 after prime vaccination with CanSino). The 0-56 days group had the highest GMT after booster injection 80.8 IU/ml (95% CI, 53.1-122.9). All groups reached seroconversion in over 80% of the participants. Anti-RBD and anti-Spike IgG titers were highest for the 56-day + 6-month booster regime. The median of IFN-γ spot counts per 106 PBMCs 14 days after the first boost and second booster was comparable for the groups receiving boosters at 28 days, 56 days, and 5 months after primary vaccination [Jin P, 2022 ].

Vaccine efficacy and effectiveness for heterologous schedule

No studies reported or assessed this outcome.

Vaccine efficacy and effectiveness for heterologous booster schedule

Immunogenicity outcomes
JSVCT115 was a phase 4 randomized trial in China that included 120 participants who received a primary CanSino vaccine and one or two Anhui Zhifei Longcom boosters. Live virus-neutralizing antibody titers against wild type SARS-CoV-2 isolate were measured 14 days after booster injection. A heterologous booster dose with ZF001 induced a significantly higher neutralizing antibody against the SARS-CoV-2 wild-type virus compared with the baseline (day 28 after prime vaccination with CanSino). The 0-56 days group had the highest GMT after booster injection 80.8 IU/ml (95% CI, 53.1-122.9). All groups reached seroconversion in over 80% of the participants. Anti-RBD and anti-Spike IgG titers were highest for the 56-day + 6-month booster regime. The median of IFN-γ spot counts per 106 PBMCs 14 days after the first boost and second booster was comparable for the groups receiving boosters at 28 days, 56 days, and 5 months after primary vaccination. [Jin P, 2022 ]

Zhang Z et al. conducted a comparative study in China, which included 904 participants with two doses of CoronaVac, who received CanSino, Anhui Zhifei or CoronVac boosters. Antibody levels and pseudovirus-based neutralizing titers were measured before and 7, 14 and 28 days after the booster vaccination. Heterologous boosting with Cansino via different routes can elicit significantly higher binding antibody levels than the other two groups. The heterologous booster regimens elicited a higher neutralizing response against the Omicron variant than the homologous regimen. The median antibody fold-increase from baseline to day 14 of Anhui Zhifei Longcom booster was 120 (IQR: 42-360). [Zhe Zhang, 2022 ]

Xu X et al was a comparative cohort study conducted in China that included serum samples from 50 participants who received booster with ZF2001 and assessed inhibitory capacity of primary and booster vaccine-induced antibodies inhibitory capacity. Heterologous booster vaccination of ZF2001 vaccine significantly restored humoral immune responses and even showed an increasing response against ancestral strain and variant B.1.351, B.1.617.2, and B.1.1.529, than homologous inactivated vaccines. [Xu X, 2022 ]

Liao Y et al was a non randomized study conducted in China that included serum samples from 480 participants who received a booster with ZF2001 at three different intervals, after a CoronaVac primary schedule and assessed live virus neutralizing antibody titers against ancestral SARS-CoV-2 strain isolate, 14 days after booster injection. After the booster, GMTs showed no significant difference among the three prime-boost interval groups. The GMTs were 42.50 (95% CI, 32.87–54.94), 60.65 (95% CI, 48.11–76.45) and 60.65 (95% C, 47.97–76.67) in the 3-4 months, 5-6 months and 7-9 months groups, respectively. [Xu X, 2022 ]

Safety of the vaccine

Safety of the vaccine in preclinical studies

Safety outcomes were not assessed in the animal studies available [An Y, 2021 ].

Safety of the vaccine in clinical trials

Main safety outcomes of the Anhui Zhifei Longcom COVID-19 vaccine

Key messages

Anhui Zhifei Longcom COVID-19 vaccine increases the risk of any adverse events.

Anhui Zhifei Longcom COVID-19 vaccine increases the risk of serious adverse events.

Any adverse event (30 days post vaccination)

The relative risk of any adverse event in the group that received Anhui Zhifei Longcom COVID-19 vaccine, versus the group that received control vaccine was 1.03 (95% CI 1 to 1.06). This means Anhui Zhifei Longcom COVID-19 vaccine increased the risk of any adverse event by 3%, compared with control vaccine.

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

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

Serious adverse events (mean follow up: 4.1 months)

The relative risk of serious adverse events in the group that received control vaccine, versus the group that received Anhui Zhifei Longcom COVID-19 vaccine was 0.82 (95% CI 0.69 to 0.97). This means Anhui Zhifei Longcom COVID-19 vaccine reduced the risk of serious adverse events by 18%, compared with control vaccine.

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

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

Summary of findings table (iSoF)

Safety of the vaccine in subgroups

Sex
Randomized trials
The differential safety of the vaccine in sex groups was not reported in the LKM-2020-NCV-GJ01 phase 3 trial [Dai L, 2022 ].

Age
Randomized trials
LKM-2020-NCV-GJ01 was a phase 3 randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of ZF2001. Adult participants (≥18 years of age) were randomized 1:1 to receive a total of three 25-μg doses (30 days apart) of ZF2001 or placebo. The primary outcome was the occurrence of symptomatic coronavirus disease 2019 (Covid-19). Participants recorded adverse events (solicited and unsolicited) that occurred 0 to 7 days after each inoculation. Reported at least one adverse event in the vaccine group (≥60 years) 28.6% participants and in the placebo group (≥60 years) 28.6% participants. [Dai L, 2022 ]

The differential safety of the vaccine across age groups was not reported in the NCV-Ⅰ-healthy phase 1 trial and the NCV-Ⅱ-healthy phase 2 trial [Yang S, 2021 ].

Children and adolescents
Randomized trials
Children and adolescents were excluded from the LKM-2020-NCV-GJ01 phase 3 trial, therefore there is no available data for this subgroup [Dai L, 2022 ].

The LKM-2021-NCV01 trial conducted in China enrolled healthy children and adolescents aged 3–17 years without: history of SARS-CoV-2 vaccination, history of COVID-19, COVID-19 at the time of the study, and contact with patients with confirmed or suspected COVID-19. Elegible participants were included in the phase 1 and phase 2 trials [Gao L, 2023 ].

Pregnancy
Pregnant women were excluded from the LKM-2020-NCV-GJ01 phase 3 trial, therefore there is no available data for this subgroup [Dai L, 2022 ].

Breastfeeding
Breastfeeding women were excluded from the LKM-2020-NCV-GJ01 phase 3 trial, therefore there is no available data for this subgroup [Dai L, 2022 ].

Immunocompromised persons
Immunocompromised persons were excluded from the LKM-2020-NCV-GJ01 phase 3 trial, therefore there is no available data for this subgroup [Dai L, 2022 ].

Safety of the vaccine post-authorization

Post-authorization studies
Comparative studies
No comparative study reported or evaluated this outcome.

Non-comparative studies
None available.

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

[China's National Medical Products Administration, 2021] China's National Medical Products Administration. China approves new type of vaccine for emergency use against COVID-19. Press release - China Daily - 2021-03-17. 2021; China's National Medical Products Administration. China approves new type of vaccine for emergency use against COVID-19. Press release - China Daily - 2021-03-17. 2021;
[INVIMA, 2022] INVIMA. Comisión revisora sala especializada de moléculas nuevas, nuevas indicaciones y medicamentos biológicos. Acta No. 01 de 2022- Primera parte. 2022; INVIMA. Comisión revisora sala especializada de moléculas nuevas, nuevas indicaciones y medicamentos biológicos. Acta No. 01 de 2022- Primera parte. 2022;
[Business Insider, 2021] Business Insider. Another Chinese Covid-19 vaccine enters late-stage human trials with a plan to produce 300 million doses annually. News. 2021; Business Insider. Another Chinese Covid-19 vaccine enters late-stage human trials with a plan to produce 300 million doses annually. News. 2021;
[An Y, 2021] An Y, Li S, Jin X et al. A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates. bioRxiv. 2021; An Y, Li S, Jin X et al. A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates. bioRxiv. 2021;
[Dai L, 2020] Dai L, Zheng T, Xu K et al. A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS. Cell. 2020;182(3). Dai L, Zheng T, Xu K et al. A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS. Cell. 2020;182(3).
[Reche PA, 2014] Reche PA, Fernandez-Caldas E, Flower DR, Fridkis-Hareli M, Hoshino Y. Peptide-based immunotherapeutics and vaccines. Journal of immunology research. 2014;2014:256784. Reche PA, Fernandez-Caldas E, Flower DR, Fridkis-Hareli M, Hoshino Y. Peptide-based immunotherapeutics and vaccines. Journal of immunology research. 2014;2014:256784.
[NMPA, 2021] NMPA. Technical guideline for the inoculation of COVID-19 vaccines. 2021; NMPA. Technical guideline for the inoculation of COVID-19 vaccines. 2021;
[PAHO, 2020] PAHO. The Immunization Program in the Context of the COVID-19 Pandemic, 26 March 2020. PAHO/FPL/IM/COVID-19/20-0005. 2020; PAHO. The Immunization Program in the Context of the COVID-19 Pandemic, 26 March 2020. PAHO/FPL/IM/COVID-19/20-0005. 2020;
[Yang S, 2021] Yang S, Li Y, Dai L et al. Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. The Lancet. Infectio Yang S, Li Y, Dai L et al. Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. The Lancet. Infectio
[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;
[Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2020] Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine (CHO Cells). clinicaltrials.gov. 2020; Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine (CHO Cells). clinicaltrials.gov. 2020;
[Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2020] Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. Clinical Study of Recombinant Novel Coronavirus Vaccine. clinicaltrials.gov. 2020; Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. Clinical Study of Recombinant Novel Coronavirus Vaccine. clinicaltrials.gov. 2020;
[Dai L, 2022] Dai L, Gao L, Tao L et al. Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults. The New England journal of medicine. 2022;386(22):2097-2111. Dai L, Gao L, Tao L et al. Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults. The New England journal of medicine. 2022;386(22):2097-2111.
[Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2022] Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. ZF2001 Booster Immunization Clinical Trials of 6 Months After the Completion of Basic Immunization. clinicaltrials.gov. 2022; Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. ZF2001 Booster Immunization Clinical Trials of 6 Months After the Completion of Basic Immunization. clinicaltrials.gov. 2022;
[Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2021] Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. ZF2001 Booster Immunization Clinical Trials of 12 Months After the Completion of Basic Immunization. clinicaltrials.gov. 2021; Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. ZF2001 Booster Immunization Clinical Trials of 12 Months After the Completion of Basic Immunization. clinicaltrials.gov. 2021;
[Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2021] Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. Immunogenicity and Safety of Booster Immunization of ZF2001 After Inoculation With Two Doses of CoronaVac. clinicaltrials.gov. 2021; Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. Immunogenicity and Safety of Booster Immunization of ZF2001 After Inoculation With Two Doses of CoronaVac. clinicaltrials.gov. 2021;
[Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., 2021] Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. Immunogenicity and Safety of Booster Immunization of ZF2001 After Inoculation With Two Doses of BBIBP-CorV. clinicaltrials.gov. 2021; Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.. Immunogenicity and Safety of Booster Immunization of ZF2001 After Inoculation With Two Doses of BBIBP-CorV. clinicaltrials.gov. 2021;
[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;
[Xin Zhao, 2021] Xin Zhao, Anqi Zheng, Dedong Li et al. Neutralization of recombinant RBD-subunit vaccine ZF2001-elicited antisera to SARS-CoV-2 variants including Delta. bioRxiv. 2021; Xin Zhao, Anqi Zheng, Dedong Li et al. Neutralization of recombinant RBD-subunit vaccine ZF2001-elicited antisera to SARS-CoV-2 variants including Delta. bioRxiv. 2021;
[Huang B, 2021] Huang B, Dai L, Wang H et al. Serum sample neutralisation of BBIBP-CorV and ZF2001 vaccines to SARS-CoV-2 501Y.V2. The Lancet. Microbe. 2021; Huang B, Dai L, Wang H et al. Serum sample neutralisation of BBIBP-CorV and ZF2001 vaccines to SARS-CoV-2 501Y.V2. The Lancet. Microbe. 2021;
[Cao Y, 2021] Cao Y, Yisimayi A, Bai Y et al. Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines. Cell research. 2021;31(7):732-741. Cao Y, Yisimayi A, Bai Y et al. Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines. Cell research. 2021;31(7):732-741.
[Zhe Zhang, 2022] Zhe Zhang, Shipo Wu, Yawei Liu et al. Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming. medRxiv. 2022; Zhe Zhang, Shipo Wu, Yawei Liu et al. Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming. medRxiv. 2022;
[Zhong J, 2022] Zhong J, Liu S, Cui T et al. Heterologous booster with inhaled Adenovirus vector COVID-19 vaccine generated more neutralizing antibodies against different SARS-CoV-2 variants. Emerging microbes & infections. 2022;:1-18. Zhong J, Liu S, Cui T et al. Heterologous booster with inhaled Adenovirus vector COVID-19 vaccine generated more neutralizing antibodies against different SARS-CoV-2 variants. Emerging microbes & infections. 2022;:1-18.
[Zhao X, 2022] Zhao X, Zhang R, Qiao S et al. Omicron SARS-CoV-2 Neutralization from Inactivated and ZF2001 Vaccines. The New England journal of medicine. 2022; Zhao X, Zhang R, Qiao S et al. Omicron SARS-CoV-2 Neutralization from Inactivated and ZF2001 Vaccines. The New England journal of medicine. 2022;
[Jin P, 2022] Jin P, Guo X, Chen W et al. Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): A randomized, observer-blinded, placebo-controlled trial. PLoS medi Jin P, Guo X, Chen W et al. Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): A randomized, observer-blinded, placebo-controlled trial. PLoS medi
[Xu X, 2022] Xu X, Hong Y, Chen E et al. Antibodies Induced by Homologous or Heterologous Inactivated (CoronaVac/BBIBP-CorV) and Recombinant Protein Subunit Vaccines (ZF2001) Dramatically Enhanced Inhibitory Abilities against B.1.351, B.1.617.2, and B.1.1.529 Variants Xu X, Hong Y, Chen E et al. Antibodies Induced by Homologous or Heterologous Inactivated (CoronaVac/BBIBP-CorV) and Recombinant Protein Subunit Vaccines (ZF2001) Dramatically Enhanced Inhibitory Abilities against B.1.351, B.1.617.2, and B.1.1.529 Variants
[Gao L, 2023] Gao L, Li Y, He P et al. Safety and immunogenicity of a protein subunit COVID-19 vaccine (ZF2001) in healthy children and adolescents aged 3-17 years in China: a randomised, double-blind, placebo-controlled, phase 1 trial and an open-label, non-randomised Gao L, Li Y, He P et al. Safety and immunogenicity of a protein subunit COVID-19 vaccine (ZF2001) in healthy children and adolescents aged 3-17 years in China: a randomised, double-blind, placebo-controlled, phase 1 trial and an open-label, non-randomised
[WHO, 2022] WHO. Statement for healthcare professionals: How COVID-19 vaccines are regulated for safety and effectiveness (Revised March 2022). WHO - Reports. 2022; WHO. Statement for healthcare professionals: How COVID-19 vaccines are regulated for safety and effectiveness (Revised March 2022). WHO - Reports. 2022;
[WHO, 2022] WHO. Coronavirus disease (COVID-19): Vaccines safety. World Health Organization - Q&A. 2022;(February). WHO. Coronavirus disease (COVID-19): Vaccines safety. World Health Organization - Q&A. 2022;(February).
[World Health Organization, 2021] World Health Organization. Safety of COVID-19 Vaccines. World Health Organization (WHO). 2021; World Health Organization. Safety of COVID-19 Vaccines. World Health Organization (WHO). 2021;
[Organización Mundial de la Salud, 2022] Organización Mundial de la Salud. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19. WHO - News. 2022; Organización Mundial de la Salud. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19. WHO - News. 2022;

Back to dashboard

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

COVID-19 vaccines

Country

Abdala of Center for Genetic Engineering and Biotechnology (CIGB)

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

	Shelf-life	Ultra-low temperature -90°C to -60°C (-130ºF to -76ºF)	Freezing -25 °C to -15°C	Refrigeration 2ºC to 8ºC (36ºF to 46ºF)	Storage after first puncture
Anhui Zhifei Longcom COVID-19 vaccine: Zifivax	Not yet available	No	No	Not yet available	Not yet available
AstraZeneca/Oxford; SK BIO; Serum Institute of India COVID-19 vaccine: Vaxzevria; Covishield (EUL)	Vaxzevria: 6 months Covishield: 9 months	No	No	Vaxzevria: 6 months Covishield: 9 months	Maximum 6 hours (2 to 8°C)
Bharat Biotech COVID-19 vaccine: Covaxin (EUL, suspended supply)	9 months	No	No	9 months	Maximum 6 hours (2 to 8°C)
CanSino COVID-19 vaccine: Convidecia	12 months	No	No	12 months	Maximum 6 hours (2 to 8°C)
CIGB (Centro de Ingeniería Genética y Biotecnología) COVID-19 vaccine: Abdala	6 months	No	No	6 months	Maximum 6 hours (2 to 8°C)
Finlay Institute of vaccines COVID-19 vaccine: Soberana 02; Soberana Plus	Soberana 02 and Soberana 02 ST: 6 months Soberana Plus and Soberana Plus ST: 4 months	No	No	Soberana 02 and Soberana 02 ST: 6 months Soberana Plus and Soberana Plus ST: 4 months	Soberana 2 and Soberana Plus: Maximum 6 hours (2 to 8°C) Soberana 2 ST and Soberana Plus ST: Use immediately
Gamaleya COVID-19 vaccine: Sputnik V; Gam-COVID-Vac; Spuntik Light	3 months	No	6 months (-18°C or below)	No	Maximum 2 hours (15 °C to 25 °C)
Janssen COVID-19 vaccine: Jcovden (EUL)	24 months	No	24 months	11 months	Maximum 6 hours (2 to 8°C)
Moderna COVID-19 vaccine: Spikevax (EUL)	9 months	No	9 months	1 month	Maximum 6 hours (2 to 25 °C)
Vacuna de Moderna contra COVID-19: Spikevax bivalent (origina + omicron BA.1/BA.5) (EUL)	9 months	Yes (-50°C to -15°C)	No	19 hours	Maximun 19 hours (2 to 8 °C)
Novavax/Serum Institute of India (SII) COVID-19 vaccine: Nuvaxovid; Covovax	9 months	No	No	9 months	Monodose: Use immediately** Multidose: Maximum 6 hours (2 to 8°C)
Pfizer-BioNTech COVID-19 vaccine: Comirnaty (EUL)	18 months	18 months	Concentrate for dispersion for injection: 2 weeks * Do not store ready-to-use or pediatric formulations under freezer conditions (-25° to -15°C).	10 weeks	Maximum 6 hours (2 to 8°C)
Vacuna de Pfizer-BioNTech contra COVID-19: Comirnaty bivalent (original + omicron BA.1) (EUL)	12 months	Yes	No	10 Weeks	Maximun 6 hours (2 a 8°C)
Sinopharm/BIBP (Beijing Institute of Biological Products) COVID-19 vaccine: Covilo (EUL)	24 months	No	No	24 months	Monodose: Use immediately** Multidose: Maximum 6 hours (2 to 8°C)
Sinopharm/WIBP (Wuhan Institute of Biological Products) COVID-19 vaccine	6 months	No	No	6 months	Monodose: Use immediately**
Sinovac COVID-19 vaccine: CoronaVac (EUL)	12 months	No	No	12 months	Monodose: Use immediately** Multidose: Maximum 6 hours (2 to 8°C)
Vector Institute COVID-19 vaccine: EpiVacCorona	Not yet available	No	No	Not yet available	Not yet available
Valneva COVID-19 vaccine	21 months	No	No	21 months	Maximum 6 hours (2 to 8°C)

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

Anhui Zhifei Longcom COVID-19 vaccine

Anhui Zhifei Longcom COVID-19 vaccine

Anhui Zhifei Longcom Biopharmaceutical; Institute of Microbiology, Chinese Academy of Sciences

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

Key messages

Main efficacy outcomes of Anhui Zhifei Longcom COVID-19 vaccine

Contracting COVID-19 (measured at least 14 days after the third dose)

Contracting severe COVID-19 (measured at least 14 days after the third dose)

Mortality

Summary of findings table (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

Main safety outcomes of the Anhui Zhifei Longcom COVID-19 vaccine

Key messages

Any adverse event (30 days post vaccination)

Serious adverse events (mean follow up: 4.1 months)

Summary of findings table (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 third dose)

Contracting severe COVID-19 (measured at least 14 days after the third dose)