Risk considerations

Adenoviruses are considered a promising vector platform for the development of vaccines for infectious disease, largely due to their safety and ability to stimulate robust cellular and/or humoral immune responses in multiple species [Coughlan L, 2020 ].

The Sputnik V COVID-19 vaccine is based on a platform that uses two adenoviral vectors, Ad26 and Ad5.
Clinical experience with the Ad26 platform consists of the Ad26.ZEBOV/MVA-BN-Filo Ebola vaccine regimen, and investigational vaccines against Zika, filovirus, HIV, HPV, malaria, and respiratory syncytial virus. Ad26-based vaccines have been used to vaccinate 193,831 participants in different clinical studies and vaccination programs, with results that have shown acceptable clinical safety profile [FDA, 2021 ].

Clinical experience with the Ad5 platform is mixed. Two studies using an Ad5 vectored HIV-1 vaccine administered found an increased risk of HIV acquisition among vaccinated men. A consensus conference about Ad5 vectors held in 2013 warned that non-HIV vaccine trials that used similar vectors in areas of high HIV prevalence could lead to an increased risk of HIV-1 acquisition in the vaccinated population. The potential mechanism for this increased susceptibility is not completely clear but theories include dampening of HIV immunity, enhancing replication of the AIDS virus, or setting up more target cells for it [Buchbinder SP, 2020 ].

On the other hand, the same effect was not detected in a trial of a recombinant adenovirus type-5 vector-based Ebola vaccine tested in a population in Sierra Leone that had a relatively high HIV prevalence.
[Zhu FC ].

It is unknown what is the impact on this risk of the genetic engineering process that is applied to Ad5 by different vaccine producers.

Efficacy of preclinical studies on the vaccine

Data on animal or other preclinical studies for this vaccine have not been published or released.

Efficacy of the vaccine in clinical trials

Main immunogenicity outcomes

Immunogenicity was evaluated in two non-randomized phase 1/2 studies (02-Gam-COVID-Vac-2020 and 03-Gam-COVID-Vac Lyo-2020) that included 76 healthy adult volunteers aged 18-60 years that received two formulations (frozen and lyophilized) of the vaccine between June 2020 and August 2020. All participants produced antibodies to SARS-CoV-2 glycoprotein (receptor binding domain-specific IgG titres at day 42: 14,703 with the frozen formulation and 11,143 with the lyophilized formulation) and neutralizing antibodies (49.25 with the frozen formulation and 45.95 with the lyophilized formulation). Seroconversion rate was 100%. Cellular responses were detected in all participants at day 28, with median cell proliferation of 2.5% CD4+ and 1.3% CD8+ with the frozen formulation, and 1.3%/1.1% with the lyophilized formulation [Logunov DY, 2020 ].

Main efficacy outcomes of Gamaleya COVID-19 vaccine

Key messages

Gamaleya COVID-19 vaccine reduces the risk of contracting COVID-19

Gamaleya COVID-19 vaccine reduces the risk of contracting severe COVID-19

Contracting COVID-19 (measured at least 21 days after the first dose)

The relative risk of contracting COVID-19 in the group that received Gamaleya COVID-19 vaccine versus the group that received placebo vaccine was 0.08 (95% CI 0.05 to 0.15). This means Gamaleya COVID-19 vaccine reduced the risk of contracting COVID-19 after the first dose in 92%, compared with the placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19. Comparison: Gamaleya COVID-19 vaccine versus placebo vaccine

In the available trial, 62 people not receiving Gamaleya COVID-19 vaccine out of 4902 presented this outcome (13 per 1000) versus 16 out of 14964 in the group that did receive it (1 per 1000). In other words, 12 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 1.2%, or that the intervention reduced the risk of contracting COVID-19 by 1.2 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 83.

Applying the GRADE approach [Logunov, Denis Y, 2021 ], we assessed the certainty of the evidence for this outcome as high.

Contracting COVID-19 after the second dose (>7d) (measured at least 7 days after the second dose)

The relative risk of contracting COVID-19 after the second dose (>7d) in the group that received versus the group that received placebo vaccine was 0.09 (95% CI 0.05 to 0.17). This means Gamaleya COVID-19 vaccine reduced the risk of contracting COVID-19 after the second dose (>7d) by 91%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19 after the second dose (>7d). Comparison: Gamaleya COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 47 people not receiving Gamaleya COVID-19 vaccine out of 4601 presented this outcome (10 per 1000) versus 47 out of 14094 in the group that did receive it (1 per 1000). In other words,10 less to 8 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 0.9%, or that the intervention reduced the risk of contracting COVID-19 after the second dose (>7d) by 0.9 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 111. Which means that 250 people need to receive the vaccine for one of them to not contracting COVID-19 after the second dose (>7d)

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

Contracting severe COVID-19 (measured at least 21 days after the first dose)

The relative risk of contracting severe COVID-19 in the group that received Gamaleya COVID-19 vaccine versus the group that received placebo vaccine was 0.01 (95% CI 0 to 0.13). This means Gamaleya COVID-19 vaccine reduced the risk of contracting severe COVID-19 in 99%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting severe COVID-19. Comparison: Gamaleya COVID-19 vaccine versus placebo vaccine

In the available trial, 20 people not receiving Gamaleya COVID-19 vaccine out of 4902 presented this outcome (4 per 1000) versus 0 out of 14964 in the group that did receive it (0 per 1000). In other words, 4 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 0.4%, or that the intervention reduced the risk of contracting severe COVID-19 by 0.4 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNTB is 250.

Applying the GRADE approach [Logunov, Denis Y, 2021 ], we assessed the certainty of the evidence for this outcome as moderate. The reason for downgrading the certainty of the evidence is the risk of bias due to losses to follow up and imprecision. No reasons for concern were detected in relation to inconsistency, indirect evidence or publication bias.

Efficacy of the vaccine in subgroups

Contracting COVID-19 (men subgroup) (measured at least 21 days after the first dose)

The relative risk of contracting COVID-19 (men subgroup) in the group that received Gamaleya COVID-19 vaccine versus the group that received placebo vaccine was 0.06 (95% CI 0.03 to 0.13). This means Gamaleya COVID-19 vaccine reduced the risk of contracting COVID-19 (men subgroup) by 94%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19 (men subgroup). Comparison: Gamaleya COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 39 people not receiving Gamaleya COVID-19 vaccine out of 3015 presented this outcome (13 per 1000) versus 39 out of 9143 in the group that did receive it (1 per 1000). In other words,13 less to 11 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 1.2%, or that the intervention reduced the risk of contracting COVID-19 (men subgroup) by 1.2 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 83. Which means that 250 people need to receive the vaccine for one of them to not contracting COVID-19 (men subgroup)

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

Contracting COVID-19 (women subgroup) (measured at least 21 days after the first dose)

The relative risk of contracting COVID-19 (women subgroup) in the group that received Gamaleya COVID-19 vaccine versus the group that received placebo vaccine was 0.13 (95% CI 0.06 to 0.27). This means Gamaleya COVID-19 vaccine reduced the risk of contracting COVID-19 (women subgroup) by 87%, compared with placebo vaccine.

Figure - Forest plot of risk ratio meta-analysis. Outcome: contracting COVID-19 (women subgroup). Comparison: Gamaleya COVID-19 vaccine versus placebo vaccine

In the trial identified in this review, 23 people not receiving Gamaleya COVID-19 vaccine out of 1887 presented this outcome (12 per 1000) versus 23 out of 5821 in the group that did receive it (2 per 1000). In other words,11 less to 9 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 1%, or that the intervention reduced the risk of contracting COVID-19 (women subgroup) by 1 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 100. Which means that 250 people need to receive the vaccine for one of them to not contracting COVID-19 (women subgroup)

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

Contracting COVID-19 (>60y) (measured at least 21 days after the first dose)

The relative risk of contracting COVID-19 (>60y) in the group that received Gamaleya COVID-19 vaccine versus the group that received placebo vaccine was 0.08 (95% CI 0.02 to 0.39). This means Gamaleya COVID-19 vaccine reduced the risk of contracting COVID-19 (>60y) by 92%, compared with placebo vaccine.

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

In the trial identified in this review, 8 people not receiving Gamaleya COVID-19 vaccine out of 533 presented this outcome (15 per 1000) versus 8 out of 1611 in the group that did receive it (1 per 1000). In other words,15 less to 9 less people per 1000 did not develop the outcome because of the vaccine. This is the same as saying that the intervention led to an absolute risk reduction of 1.4%, or that the intervention reduced the risk of contracting COVID-19 (>60y) by 1.4 percentage points. Another way of presenting the same information about the absolute effects is the number needed to treat for an additional beneficial/harmful outcome (NNTB/H), the number of participants who need to receive the intervention for one of them to experience the outcome. In this case, the NNT is 71. Which means that 250 people need to receive the vaccine for one of them to not contracting COVID-19 (>60y)

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

Summary of findings (iSoF)

Efficacy and effectiveness of the vaccine in subgroups

Sex

Randomized trials

The proportion of females in the RESIST trial was 38.8% (7,708 out of 19,866 participants) [Logunov, Denis Y, 2021 ]. The relative risk of contracting COVID-19 in females that received Sputnik V COVID-19 vaccine versus the group that received placebo vaccine was 0.08 (95% CI 0.02 to 0.39). This means Sputnik V COVID-19 vaccine reduced the risk of contracting COVID-19 in 92%, compared with the placebo vaccine. This estimate is not statistically different from the estimate for this outcome in the overall population of the trial.

Age

Randomized trials 

The RESIST trial [Logunov, Denis Y, 2021 ] included 2,144 participants older than 60 years (1,611 in the vaccine group and 533 in the placebo group. The relative risk of contracting COVID-19 in participants older than 60 years that received Sputnik V COVID-19 vaccine versus the group that received placebo vaccine was 0.08 (95% CI 0.02 to 0.39). This means Sputnik V COVID-19 vaccine reduced the risk of contracting COVID-19 in 92%, compared with the placebo vaccine. This estimate is not statistically different from the estimate for this outcome in the overall population of the trial.

Children and adolescents

Randomized trials

Children were excluded from the RESIST trial [Logunov, Denis Y, 2021 ].

Pregnancy

Randomized trials

Pregnant females were excluded from the RESIST trial [Logunov, Denis Y, 2021 ].

Breastfeeding

Randomized trials

Women who were breastfeeding were excluded from the RESIST trial [Logunov, Denis Y, 2021 ].

Immunocompromised persons
Randomized trials
Immunocompromised persons were excluded from the RESIST trial [Logunov, Denis Y, 2021 ].

Other comparative studies
Gushcin et al was a retrospective cohort study to assess the effectiveness of the standard Sputnik V vaccination regimen in 24,423 HIV+ Moscow residents during spring - summer 2021 with estimation of hospitalization and severe illness rates in vaccinated and unvaccinated patients. Data were extracted from the Moscow anti-COVID-19 vaccination and COVID-19 incidence Registries. The main results showed that vaccine effectiveness was 79.42%, avoiding hospitalization in 90.12% cases and protecting from the development of moderate or severe disease in 97.06%. For delta variant in this group the efficiency was 65.35%, avoiding the need for hospitalization in 75.77% cases and protecting from the development of moderate or severe disease in 93.05% of patients [Gushchin VA, 2022 ].

Vaccine effectiveness (other comparative studies)

Contracting COVID-19
Mirahmadizadeh A et al. was a cohort study conducted in Iran. The study enrolled 1,882,148 participants: 881,638 vaccine group; 1,000,510 control group. Based on data derived from administrative repositories during mass-vaccination campaigns or programs between February 09, 2021, and the end of follow-up on October 22, 2021; the study results showed vaccine effectiveness of 74.7% (95%CI 71.0 to 78.4%) against infection, 67.5% (95%CI 59.5 to 75.6%) against hospitalization and 100% against death. [Alireza Mirahmadizadeh, 2022 ]

Rearte A et al. was a case-control study conducted in Argentina. The study included 687,167 individuals in the analysis of the rAd26-rAd5 vaccine: 218,417 in the case group and 468,750 in the control group. The study assessed the effectiveness of three vaccines (rAd26-rAd5, ChAdOx1 nCoV-19, and BBIBP-CorV) on SARS-CoV-2 infection and risk of death in people with RT-PCR-confirmed COVID-19, using data from the National Surveillance System (SNVS 2.0). All individuals aged 60 years or older reported to SNVS 2.0 as being suspected to have COVID-19 who had disease status confirmed with RT-PCR were included in the study. The odds ratio of the rAd26-rAd5 vaccine on the risk of SARS-CoV-2 infection in individuals with only one dose was OR 0.61 (95% CI 0.60 to 0.61). After the second dose was OR 0.36 (95% CI 0.0.35 to 0.37). [Rearte A, 2022 ]

Petrovic V et al. was a study conducted in Serbia, including data from 7,037 participants with two Sputnik V vaccines and 241,166 controls. Based on data from the surveillance registry from Vojvodina and the nationwide COVID-19 vaccine registry, participants aged 60 and above, between December 24, 2020 and April 28, 2021. The overall effectiveness of Sputnik was 95% (95% CI 92.4 to 96.7) and 94.7% (95% CI 91.6 to 96.7)  against mild COVID-19. [Petrovi? V, 2022 ]

Horvath et al. was a study conducted in Hungary, including data from 2,808,893 participants with two Sputnik V vaccines. Based on data from the Hungarian Notifiable Disease Surveillance System, between 2021 up to January 24 2022. The overall efectiveness of the was 1.1% (95% CI -11.4 to 12.1) in the 18-24 age group, 49.5% (95% CI 46.6 to 52.3) in the 25-49 age group, 68% (95% CI 64.4 to 71.3) in the 50-59 age group, 71.1% (95% CI 67.3 to 74.4) in the 60-69 age group, 75.1% (95% CI 71.4 to 78.3) in the 70-79 age group  and 61.1% (95% CI 56 to 65.7) in participants aged 80 and above. [Krisztina J. Horvath, 2022 ]

Sukhikh GT et al was a comparative cohort study in Russia to estimate vaccine effectiveness (VE) against COVID-19, before and during the Delta predominance period. The study included 1,624 participants with at least one Sputnik dose, 819 cases and 805 controls, based on data from medical workers employed at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health. Data from November 2020 to February 2022. The overall VE was 89.1% (95% CI, 86.9% to 91%) for the entire period irrespective of the number of doses. [Sukhikh GT, 2022 ]

Bello-Chavolla OY et al was a retrospective cohort study conducted in Mexico, including 793,487 vaccinated and 4,792,388 unvaccinated individuals. This study estimated vaccine effectiveness (VE) against infection and hospitalization, based on data from the COVID-19 surveillance system between December 2020 and September 2021. Among 39,952 participants vaccinated with Sputnik, VE against infection was 78.75% (95% CI, 78.17% to 79.31%), and VE against hospitalization was 81.38% (95% CI, 79.45% to 83.13%) [Bello-Chavolla OY, 2023 ].

Contracting severe COVID-19
Mukherjee S et al. was a comparative study conducted in Bahrain. The study enrolled 1,242,279 participants that received the Sputnik-V COVID-19 vaccine. Based on data from the centralized country-specific Information system (ISEHA) with all medical history of individuals and is, anonymized electronic health records were retrieved for the study period December 9th, 2020 - July 17 202. The outcome was measured starting at ≥ 14 days after vaccination. Results showed a vaccine hospitalization rate of 2.24%, an ICU admission rate of 0%, and a death rate of 0.09%. [Mukherjee S, 2021 ]

Barchuk et al. was a case-control study conducted in Russia, to assess the vaccine effectiveness (VE) against referral to hospital. The study recruited 13,893 participants (1,291 complete vaccination status and 495 were referred to the hospital) who received the Sputnik-V or Sputnik light COVID-19 vaccines. Based on individual-level patient data from two outpatient triage centers of the Medical Institute named after Berezin Sergey (MIBS) between July 3rd and August 9th, 2021. The adjusted VE against referral to the hospital was 81% (95% CI, 68% to 88%) for complete vaccination. The VE against referral to the hospital was more pronounced in women (84%, 95% CI, 66% to 92%) compared to men (76%, 95% CI, 51% to 88%). Vaccine protective effect increased with increasing lung injury categories, from 54% (95% CI, 48% to 60%) against any sign of lung injury to 76% (95% CI, 59% to 86%) against more than 50% lung involvement. A sharp increase was observed in the probability of hospital admission with age for non-vaccinated patients in relation to an almost flat relationship for the completely vaccinated group. [Barchuk A, 2022 ]

Mirahmadizadeh A et al. was a cohort study conducted in Iran. The study enrolled 1,882,148 participants: 881,638 vaccine group; 1,000,510 control group. Based on data derived from administrative repositories during mass-vaccination campaigns or programs between February 09, 2021, and the end of follow-up on October 22, 2021; the study results showed vaccine effectiveness of 74.7% (95%CI 71.0 to 78.4%) against infection, 67.5% (95%CI 59.5 to 75.6%) against hospitalization and 100% against death. [Alireza Mirahmadizadeh, 2022 ]

Petrovic V et al. was a study conducted in Serbia, including data from 7,037 participants with two Sputnik V vaccines and 241,166 controls. Based on data from the surveillance registry from Vojvodina and the nationwide COVID-19 vaccine registry, participants aged 60 and above, between December 24, 2020 and April 28, 2021. The effectiveness of Sputnik V was 95.9% (95% CI 89 to 98.5) against severe COVID-19. [Petrovi? V, 2022 ]

Heidarzadeh et al was a test-negative case-control study to estimate the effectiveness of COVID-19 vaccines against hospitalization and death in the Guilan Province of Iran, from May to December 2021. This study included population aged 5 years and above by extracting information from local databases (MCMC and SIB). The total study population was 42,084 including 19,500 cases and 22,586 controls. For the Sputnik + Sputnik schedule, Vaccine Effectiveness (VE) against hospitalization (temporary admission) was 76% (95% CI, -77% to 97%) within 1-30 days and 95% (95% CI, 79% to 99%) ≥ 151 days after the second dose. VE against hospitalization (regular admission) was 84% (95% CI, 57% to 94%) within 1-30 days and 93% (95% CI, 88% to 96%) ≥ 151 days after the second dose. VE against hospitalization (ICU admission) was 51% (95% CI, -2.58 to 94%) within 91-120 days and 18% (95% CI, -1.36 to 71%) ≥ 151 days after the second dose. VE against death was 25% (95% CI, -1.49 to 78%) within 31-60 days and 93% (95% CI, 47% to 99.1%) ≥ 151 days after the second dose. [Heidarzadeh A, 2022 ]

Bello-Chavolla OY et al was a retrospective cohort study conducted in Mexico, including 793,487 vaccinated and 4,792,388 unvaccinated individuals. This study estimated vaccine effectiveness (VE) against infection and hospitalization, based on data from the COVID-19 surveillance system between December 2020 and September 2021. Among 39,952 participants vaccinated with Sputnik, VE against infection was 78.75% (95% CI, 78.17% to 79.31%), and VE against hospitalization was 81.38% (95% CI, 79.45% to 83.13%) [Bello-Chavolla OY, 2023 ].

Transmission
No studies reported or assessed this outcome.

Efficacy and effectiveness against SARS-CoV-2 variants

Immunogenicity outcomes

Alpha (B.1.1.7)

Satoshi Ikegame et al. was a non-comparative study (neutralizing capacity from recipients' sera), which included 12 recipients of the Sputnik V vaccine. The study reported data from 1 month post immunization. The results showed that the Gamaleya Sputnik V Ad26 / Ad5 vaccine sera effectively neutralized the S: WT and S: B.1.1.7 viruses; although with highly variable titles (1 / IC50 GMT 49.4, 23.4 to 105) [Satoshi Ikegame, 2021 ].

María M et al. conducted a non-comparative study (neutralizing capacity from recipients' sera), which included 118 recipients of the Sputnik V vaccine. The study reported data from 42 days post immunization. The results showed a decrease in neutralizing activity against the Alpha variant in comparison with the Wuhan related pseudotyped virus (2.5-fold) [Gonzalez Lopez Ledesma MM et al., 2021 ].

Gushchin VA et al. It was a non-comparative study (neutralizing capacity from recipients' sera), which included 13 recipients of the Sputnik V vaccine. The study reported data from 1 month post immunization. The results showed that the neutralizing properties of Sputnik V induced sera are not changed by B.1.1.7 variant [Gushchin VA, 2021 ].

Beta (B.1.351)

Satoshi Ikegame et al. was a non-comparative study (neutralizing capacity from recipients' sera), which included 12 recipients of the Sputnik V vaccine. The study reported data from 1 month post immunization. The results showed that the Gamaleya Sputnik V Ad26 / Ad5 recipients sera exhibited moderate and markedly reduced neutralization titers against S: B.1.351 (Median/IQR = 0.4965 / 0.2880 to 1.186) (Median 6.8- and 2.8-fold) [Satoshi Ikegame, 2021 ].

María M et al. conducted a non-comparative study (neutralizing capacity from recipients' sera), which included 118 recipients of the Sputnik V vaccine. The study reported data from 42 days post immunization. The results showed Gamaleya Sputnik V Ad26 / Ad5 vaccine sera were less effective at neutralizing the Beta (19.2-fold) [Gonzalez Lopez Ledesma MM et al., 2021 ].

Gushchin VA et al. It was a non-comparative study (neutralizing capacity from recipients' sera), which included 13 recipients of the Sputnik V vaccine. The study reported data from 1 month post immunization. The results showed that the three-fold decrease in the viral-neutralizing activity of B.1.351 variant was recorded for sera of the patients vaccinated with Sputnik V for Spike-pseudotyped lentivirus and a 3.1-fold decrease for a live viral isolat [Gushchin VA, 2021 ].

Byazrova et al conducted a comparative study in Russia that recruited 58 individuals who were all vaccinated with two injections of Gam-COVID-Vac (first Ad26, second Ad5) between January and April 2021. All received their booster vaccination, cohort 1 (n=48) received Gam-COVID-Vac (Ad26) and cohort 2 (n=10) received Pfizer-BioNTech. Neutralizing antibodys (NAb) against Alfa variant in the homologous boost showed a 4.0-fold increase. In the heterologous vaccination group receiving an mRNA-based boost, anti-SARS-CoV-2 NAb levels against Alfa showed a 31.6-fold increase. [Byazrova MG, 2022 ]

Gamma (P.1)

Blanco S et al. was a cohort study conducted in Argentina. The study enrolled 285 participants, mainly health-care workers, assessing vaccine immunogenicity outcomes against gamma variant measured 14 and 42 days after-vaccination. The study results showed Median (IQR) neutralizing titres of 1/80 (1/20 - 1/320) [Blanco S, 2021 ].

Gonzalez Lopez Ledesma MM et al. included 118 Sputnik V vaccine recipients. Data were collected 21, 42, 120, and 180 days after the first vaccination. The study showed that There was a reduction in neutralizing activity compared to Wuhan virus. Neutralizing activity fold change compared to Wuhan virus was -2.5 (42 days) and -2.9 (120 days) against the Alpha variant; -19.2 (42 days) and -9.7 (120 days) against the Delta variant; -13.8 (42 days) and -4.2 (120 days) against the Gamma variant; and finally, -5.1 (42 days) and -3.4 (120 days) against the Delta variant [Gonzalez Lopez Ledesma MM, 2022 ].

Delta (B.1.617.2)

Gonzalez Lopez Ledesma MM et al. included 118 Sputnik V vaccine recipients. Data were collected 21, 42, 120, and 180 days after the first vaccination. The study showed that There was a reduction in neutralizing activity compared to Wuhan virus. Neutralizing activity fold change compared to Wuhan virus was -2.5 (42 days) and -2.9 (120 days) against the Alpha variant; -19.2 (42 days) and -9.7 (120 days) against the Delta variant; -13.8 (42 days) and -4.2 (120 days) against the Gamma variant; and finally, -5.1 (42 days) and -3.4 (120 days) against the Delta variant [Gonzalez Lopez Ledesma MM, 2022 ].

Byazrova et al conducted a comparative study in Russia that recruited 58 who were all vaccinated with two doses of Gam-COVID-Vac (first Ad26, second Ad5) between January and April 2021. All received their booster vaccination, cohort 1 (n=48) received Gam-COVID-Vac (Ad26) and cohort 2 (n=10) received Pfizer-BioNTech. Neutralizing antibodies (NAb) against Delta variant in the homologous boost showed a 2.3-fold increase. In the heterologous vaccination group receiving an mRNA-based boost, anti-SARS-CoV-2 NAb levels against Delta showed a 15.2-fold increase. [Byazrova MG, 2022 ]

Omicron (B.1.1.529.1)
Byazrova et al conducted a comparative study in Russia that recruited 58 individuals. All participants were vaccinated with two doses of Gam-COVID-Vac (first Ad26, second Ad5) between January and April 2021. All received their booster vaccination, cohort 1 (n=48) received Gam-COVID-Vac (Ad26) and cohort 2 (n=10) received Pfizer-BioNTech. Neutralizing antibodies (NAb) against the Omicron variant in the homologous boost showed a 3.9-fold increase. In the heterologous vaccination group receiving an mRNA-based boost, anti-SARS-CoV-2 NAb levels against Omicron showed a 47.0-fold increase. [Byazrova MG, 2022 ]

Effectiveness outcomes

Delta (B.1.617.2)

Anton Barchuk et al. was a case-control study conducted in Russia. The study enrolled 3,945 participants: 2,555 vaccine group; 1,390 control group and assessed the effectiveness of Gamaleya Sputnik vaccine against symptomatic infection with Delta variant during the outbreak caused by the Delta VOC in October 2021 in St. Petersburg, Russia. The study results showed an effectiveness against symptomatic infection of 50% (95% CI 30 to 64) with one dose and 58% (95% CI 50 to 64) with Two doses [Anton Barchuk, 2022 ].

Olga Matveeva et al. was a retrospective cohort study conducted in Russia. The study included over 300,000 cases of COVID-19 and assesed the effectiveness of Sputnik V vaccine against severe infection and death in Delta variant cases during June and July 2021 in Moscow. The study showed an effectiveness against severe infection of 89% (95% CI 81 to 94) in the 18-50 age group, 76% (95% CI 70 to 81) in the 51-70 age group and 42% (95% CI 32 to 51) in the 70+ age group. [Matveeva O, 2022 ].

Horvath et al. was a study conducted in Hungary, including data from 2,808,893 participants with two Sputnik V vaccines. Based on data from the Hungarian Notifiable Disease Surveillance System, between 2021 up to January 24 2022 during the Delta variant surge period. The overall effectiveness was 1.1% (95% CI -11.4 to 12.1) in the 18-24 age group, 49.5% (95% CI 46.6 to 52.3) in the 25-49 age group, 68% (95% CI 64.4 to 71.3) in the 50-59 age group, 71.1% (95% CI 67.3 to 74.4) in the 60-69 age group, 75.1% (95% CI 71.4 to 78.3) in the 70-79 age group, and 61.1% (95% CI 56 to 65.7) in participants aged 80 and above [Krisztina J. Horvath, 2022 ].

Barchuk et al conducted a test-negative case-control study in Russia, to estimate vaccine effectiveness (VE) against any volume of involved lung parenchyma and severe lung injury detected on computer tomography and associated with COVID-19, during Delta and Omicron. Among 23,996 patients in the primary analysis, 13,372 (55.7%) had any lung injury, and 338 (1.4%) had severe lung injury. Effectiveness of vaccination against any lung injury, according to Delta period were 59% (95% CI, 55–62) for two-dose Gam-COVID-Vac (Sputnik V) and 57% (95% CI, 48–64) for three-dose Gam-COVID-Vac (booster). [Barchuk A, 2022 ]

Barchuk A et al was a population-based case-control study conducted in Russia. This study aimed to estimate the efectiveness of the Russian COVID-19 vaccines against symptomatic SARS-CoV-2 during the recent outbreak caused by the Delta VOC in October 2021. 1,254 cases and 2,747 controls were included in the final analysis. Adjusted vaccine effectiveness against symptomatic PCR-confrmed SARS-CoV-2 for individuals with 2 doses of Sputnik V was 56% (95% CI 48 to 63) and 49% (95% CI 29 to 63) for participants with one dose of Sputnik Light. Adjusted vaccine effectiveness against symptomatic PCR-confrmed SARS-CoV-2 for individuals vaccinated with EpiVacCorona was -58% (95% CI -225 to 23).  Adjusted vaccine effectiveness against lung injury for individuals with 2 doses of Sputnik V was 69% (95% CI 62 to 74) and 58% (95% CI 37 to 72) for participants with one dose of Sputnik Light. Adjusted vaccine effectiveness against lung injury for individuals vaccinated with EpiVacCorona was -30% (95% CI -165 to 37). [Barchuk A, 2022 ]

Sukhikh GT et al conducted a comparative cohort study in Russia, to estimate vaccine effectiveness (VE) against COVID-19, before and during delta predominance. The study included 1,624 participants with at least one Sputnik dose, 819 cases and 805 controls, based on data from medical workers employed at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health. From November 2020 to February 2022. The VE during the delta period was 78.8% (95% CI, 49.2–91.1) after one dose, 81.8% (95% CI, 73.1–87.6) after two doses and 100% after three or four doses. [Sukhikh GT, 2022 ]

Omicron (B.1.1.529.1)

Barchuk et al conducted a test-negative case-control study in Russia, to estimate vaccine effectiveness (VE) against any volume of involved lung parenchyma and severe lung injury detected on computer tomography and associated with COVID-19, during Delta and Omicron. Among 23,996 patients in the primary analysis, 13,372 (55.7%) had any lung injury, and 338 (1.4%) had severe lung injury. Effectiveness of vaccination against any lung injury, according to Omicron period were 38% (95% CI, 32–44) for two-dose Gam-COVID-Vac (Sputnik V), 57% (95% CI, 51–63) for three-dose Gam-COVID-Vac (booster) and 5% (95% CI, −43 to 37) for EpiVacCorona. [Barchuk A, 2022 ]

Soledad Gonzalez et al was a test-negative, case-control study conducted in Argentina. The study included 422,144 individuals ≥50 years: 221,933 with positive test and 200,211 with negative test. The aim of the study was to estimate the protection against laboratory-confirmed SARS-CoV-2 infection, hospitalisations, and death after homologous or heterologous third-dose (booster) in individuals with primary vaccination schemes with rAd26-rAd5, ChAdOx1nCoV-19, BBIBP-CorV or heterologous combinations, during the period of Omicron BA.1 predominance. Odds ratio of booster dose against confirmed SARS-CoV-2 infections were 0.64 (95% CI 0.61 to 0.67) for ChAdOx1 primary schedule and mRNA booster (≤ 60 days), 0.97 (95% CI 0.93 to 1.01) for ChAdOx1 primary schedule and vectored booster (≤ 60 days), 0.62 (95% CI 0.55 to 0.69) for BBIBP-CorV primary schedule and mRNA booster (≤ 60 days), 0.71 (95% CI 0.67 to 0.75) for BBIBP-CorV primary schedule and vectored booster (≤ 60 days), 0.66 (95% CI 0.63 to 0.69) for rAd26-rAd5 primary schedule and mRNA booster (≤ 60 days) and 0.94 (95% CI 0.90 to 0.97) for rAd26-rAd5 primary schedule and vectored booster (≤ 60 days). Odds ratio of booster dose against hospitalizations were 0.14 (95% CI 0.03 to 0.77) for ChAdOx1 primary schedule and mRNA booster (≤ 60 days), 0.28 (95% CI 0.22 to 0.37) for ChAdOx1 primary schedule and vectored booster (≤ 60 days), 0.22 (95% CI 0.09 to 0.51) for BBIBP-CorV primary schedule and mRNA booster (≤ 60 days), 0.24 (95% CI 0.17 to 0.34) for BBIBP-CorV primary schedule and vectored booster (≤ 60 days), 0.24 (95% CI 0.17 to 0.32) for rAd26-rAd5 primary schedule and mRNA booster (≤ 60 days) and 0.34 (95% CI 0.28 to 0.41) for rAd26-rAd5 primary schedule and vectored booster (≤ 60 days). [Soledad Gonzalez, 2022 ]

Vaccine efficacy and effectiveness for booster dose

Immunogenicity outcomes
AlMadhi et al. conducted a phase II non-randomized, non-blinded observational community trial to investigate the reactogenic and immunogenetic response of heterologous (Pfizer; 428 participants) versus homologous (Sputnik V; 351 participants) COVID-19 vaccine boosting of participants who previously received two doses of Sputnik V. Adverse events were more frequent in the heterologous arm (p<0.001). No serious adverse events were reported in either arm. Amongst 577 individuals who completed the study, Anti-S antibodies were 14.8 times higher after heterologous boosting, and 3.1 times higher after homologous boosting (p<0.001). Similarly, heterologous boosting showed a 2-fold increase in neutralizing antibodies, compared to a 1.6-fold increase in homologous boosting (p<0.001). [Marwa Almadhi, 2022 ]

Byazrova et al conducted a comparative study in Russia that recruited 58 individuals. All participants were vaccinated with two doses of Gam-COVID-Vac (first Ad26, second Ad5) between January and April 2021. All received their booster vaccination, cohort 1 (n=48) received Gam-COVID-Vac (Ad26) and cohort 2 (n=10) received Pfizer-BioNTech. Gam-COVID-Vac revaccination resulted in a 2.5-fold increase in RBD-specific IgG levels (median = 582 ng/mL, p <0 .0001) and seroprevalence 94% (45/48). Neutralizing antibodies against Alfa, Epsilon, Delta, and Omicron variants of concern in the homologous boost showed a fold increase of 4.0, 2.4, 2.3, and 3.9, respectively.[Byazrova MG, 2022 ]

Effectiveness outcomes
Barchuk et al conducted a test-negative case-control study in Russia, to estimate vaccine effectiveness (VE) against any volume of involved lung parenchyma and severe lung injury detected on computer tomography and associated with COVID-19, during Delta and Omicron predominance periods. Among 23,996 patients in the primary analysis, 13,372 (55.7%) had any lung injury, and 338 (1.4%) had severe lung injury. The VE adjusted for age, sex, and triage center against any lung injury were 56% (95% CI 54% to 59%) for two-dose Gam-COVID-Vac (Sputnik V) and 71% (95% CI, 68% to 74%) for three-dose Gam-COVID-Vac (booster). VE estimates against severe lung injury were 76% (95% CI, 67% to 82%) for two-dose Gam-COVID-Vac (Sputnik V) and 87% (95% CI, 76% to 93%) for three-dose Gam-COVID-Vac. [Barchuk A, 2022 ]

Sukhikh GT et al conducted a comparative cohort study in Russia to estimate vaccine effectiveness (VE) against COVID-19, before and during the Delta predominance period. The study included 1,624 participants with at least one Sputnik dose, 819 cases, and 805 controls, based on data from medical workers employed at the Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology of the Ministry of Health. Data from November 2020 to February 2022. The VE during the Delta period was 100% after three or four doses. [Barchuk A, 2022 ]

Vaccine efficacy and effectiveness for heterologous schedule

Immunogenicity outcomes

Macchia et al, was a non-inferiority randomized clinical trial conducted in Argentina. The study compared the immune response generated by homologous Sputnik V regimen to the heterologous regimens of Sputnik V vaccine with either Moderna, Sinopharm BIBP or AstraZeneca vaccines. The study recruited 540 individuals with no history of COVID-19 infection who had received a first dose of the Sputnik V vaccine (component rAd26) at least 30 days prior. Participants were randomized to receive a second dose of either Sputnik V (component rAd26 or rAd5), AstraZeneca, Moderna or Sinopharm BIBP vaccines. The study showed all but the Moderna regimen were statistically inferior to the standard Sputnik V regimen (rAd26/rAd5). The Moderna regimen showed a 3.53 fold increase in antibody concentrations compared to the standard Sputnik V regimen [Macchia A, 2022 ].

Vaccine efficacy and effectiveness for heterologous booster schedule

Immunogenicity outcomes
AlMadhi et al. conducted a phase II non-randomized, non-blinded observational community trial to investigate the reactogenic and immunogenetic response of heterologous (Pfizer; 428 participants [54.9%]) versus homologous (Sputnik V; 351 participants [45.1%]) COVID-19 vaccine boosting of participants who previously received two doses of Sputnik V. Adverse events were more frequent in the heterologous arm (p<0.001). No serious adverse events were reported in either arm. Amongst 577 individuals who completed the study, Anti-S antibodies were 14.8 times higher after heterologous boosting, and 3.1 times higher after homologous boosting (p<0.001). Similarly, heterologous boosting showed a 2-fold increase in neutralizing antibodies, compared to a 1.6-fold increase in homologous boosting (p<0.001). [Marwa Almadhi, 2022 ].

Byazrova et al conducted a comparative study in Russia that recruited 58 individuals who were all vaccinated with two doses of Gam-COVID-Vac (first Ad26, second Ad5) between January and April 2021. All received their booster vaccination, cohort 1 (n=48) received Gam-COVID-Vac (Ad26) and cohort 2 (n=10) received Pfizer-BioNTech. A pronounced increase in RBD-specific IgGs was observed in the heterologous vaccination group (8.7-fold change, p = 0.0039) [Byazrova MG, 2022 ]

Effectiveness outcomes
Gonzalez  S et al was a test-negative, case-control study conducted in Argentina. The study included 422,144 individuals ≥50 years: 221,933 with a positive test and 200,211 with a negative test. The aim of the study was to estimate the protection against laboratory-confirmed SARS-CoV-2 infection, hospitalizations, and death after homologous or heterologous third-dose (booster) in individuals with primary vaccination schemes with rAd26-rAd5, ChAdOx1nCoV-19, BBIBP-CorV or heterologous combinations, during the period of Omicron BA.1 predominance. The odds ratio of booster dose against confirmed SARS-CoV-2 infections were 0.64 (95% CI 0.61 to 0.67) for ChAdOx1 primary schedule and mRNA booster (≤ 60 days), 0.97 (95% CI 0.93 to 1.01) for ChAdOx1 primary schedule and vectored booster (≤ 60 days), 0.62 (95% CI 0.55 to 0.69) for BBIBP-CorV primary schedule and mRNA booster (≤ 60 days), 0.71 (95% CI 0.67 to 0.75) for BBIBP-CorV primary schedule and vectored booster (≤ 60 days), 0.66 (95% CI 0.63 to 0.69) for rAd26-rAd5 primary schedule and mRNA booster (≤ 60 days) and 0.94 (95% CI 0.90 to 0.97) for rAd26-rAd5 primary schedule and vectored booster (≤ 60 days). The odds ratio of booster dose against hospitalizations were 0.14 (95% CI 0.03 to 0.77) for ChAdOx1 primary schedule and mRNA booster (≤ 60 days), 0.28 (95% CI 0.22 to 0.37) for ChAdOx1 primary schedule and vectored booster (≤ 60 days), 0.22 (95% CI 0.09 to 0.51) for BBIBP-CorV primary schedule and mRNA booster (≤ 60 days), 0.24 (95% CI 0.17 to 0.34) for BBIBP-CorV primary schedule and vectored booster (≤ 60 days), 0.24 (95% CI 0.17 to 0.32) for rAd26-rAd5 primary schedule and mRNA booster (≤ 60 days) and 0.34 (95% CI 0.28 to 0.41) for rAd26-rAd5 primary schedule and vectored booster (≤ 60 days). [Soledad Gonzalez, 2022 ]

Safety of the vaccine in preclinical studies

Data on animal or other preclinical studies for this vaccine have not been published or released.

Safety of the vaccine in clinical trials

Main safety outcomes of Gamaleya COVID-19 vaccine

The safety of Main immunogenicity outcomes presented here was estimated from the report of the RESIST trial, the only phase 3 randomized trial with available data at this moment [Logunov, Denis Y, 2021 ], based on data from 12,296 participants.

Any adverse event

The risk of any adverse event has not been reported, so it was not possible to estimate the effect for this outcome [Logunov, Denis Y, 2021 ].

Non-serious adverse events

The total number of non-serious adverse events was not reported, so it was not possible to estimate the effect for this outcome [Logunov, Denis Y, 2021 ].

The most common adverse events were flu-like illness, injection site reactions, headache, and asthenia.

Serious adverse event

The relative risk of serious adverse events in the group that received Gamaleya COVID-19 vaccine versus the group that received placebo vaccine was 0.65 (95% CI 0.39 to 1.07). This means that the group that received Gamaleya COVID-19 vaccine within the trial reported 35% less serious adverse events than the group that received the placebo vaccine.

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

In the available trial, 23 people not receiving Gamaleya COVID-19 vaccine out of 5435 presented this outcome (4 per 1000) versus 45 out of 16427 in the group that did receive it (3 per 1000). In other words, the group receiving the vaccine reported less serious adverse effects than the group that received the placebo vaccine.

Applying the GRADE approach [Logunov, Denis Y, 2021 ], we assessed the certainty of the evidence for this outcome as low. The reasons for downgrading the certainty of the evidence were the risk of bias due to losses to follow up and the imprecision of the result as a consequence of the low number of events. No reasons for concern were detected in relation to inconsistency, indirect evidence or publication bias.

Summary of findings (iSoF)

Safety of the vaccine in subgroups

Sex

Randomized trials

In the RESIST trial. the relative risk of contracting COVID-19 in the women subgroup was 0.13 (95% CI 0.06 to 0.27). This means Gamaleya COVID-19 vaccine reduced the risk of contracting COVID-19 in women by 87%, compared with placebo vaccine. The relative risk of contracting COVID-19 in the men subgroup was 0.06 (95% CI 0.03 to 0.13). This means Gamaleya COVID-19 vaccine reduced the risk of contracting COVID-19 in menby 94%, compared with placebo vaccine [Logunov, Denis Y, 2021 ].

Age

Randomized trials

The proportion of participants >60 years of age in the RESIST trial was 10.8% (2144 out of 19866 participants) [Logunov, Denis Y, 2021 ]. There were 1369 participants older than 60 years included in the safety analysis.The most common adverse events were flu-like illness in 156 (15.2%) and local reaction in 56 (5.4%) of 1029 participants in the vaccine group, while 30 (8.8%) and four (1.2%) of 340 participants presented the adverse events in the placebo group, respectively.

Children and adolescents

Randomized trials

Children were excluded from the RESIST trial [Logunov, Denis Y, 2021 ].

Pregnancy

Randomized trials

Pregnant women were excluded from the RESIST trial [Logunov, Denis Y, 2021 ].

Breastfeeding

Randomized trials

Breastfeeding women were excluded from the RESIST trial [Logunov, Denis Y, 2021 ].