Log in to MyACC
rAd26 and rAd5 Vector-Based Heterologous Prime-Boost COVID-19 Vaccine
Quick Takes
- Gam-COVID-Vac is a combined adenoviral vector vaccine against SARS-CoV-2; with each dose using a different vector carrying the gene coding for the spike protein.
- In this interim analysis of a phase 3 trial with 21,977 participants including over 2,000 participants aged >60 years, Gam-COVID-Vac was safe and 91.6% effective in preventing COVID-19 at a median follow-up time of 48 days post-dose 1.
- Gam-COVID-Vac has been approved for storage at 2-8°C, which facilitates distribution.
Study Questions:
Is the heterologous recombinant adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine Gam-COVID-Vac (Sputnik V) safe and effective in preventing coronavirus disease 2019 (COVID-19) 21 days after the first dose?
Methods:
Gam-COVID-Vac is a combined vector vaccine, based on rAd type 26 (rAd26) and rAd type 5 (rAd5)—both of which carry the gene for SARS-CoV-2 full-length glycoprotein S (rAd26-S and rAd5-S). rAd26-S and rAd5-S are administered intramuscularly separately with a 21-day interval.
This study provides interim efficacy and safety results of a randomized, double-blind, placebo-controlled, phase 3 trial performed at 25 hospitals and polyclinics in Moscow, Russia. We included participants aged ≥18 years, with negative SARS-CoV-2 polymerase chain reaction (PCR) and IgG and IgM tests, no infectious diseases in the 14 days before enrollment, and no other vaccinations in the 30 days before enrollment. Pregnant women and immunosuppressed patients were excluded. Participants were randomly assigned (3:1) to receive vaccine or placebo, with stratification by age group (18–30 years, 31–40 years, 41–50 years, 51–60 years, and >60 years). A PCR test was done on the day of the second dose (day 21) for the diagnosis of symptomatic and asymptomatic COVID-19 cases. The primary outcome was the proportion of participants with PCR-confirmed COVID-19 from day 21 after receiving the first dose. The primary outcome was assessed in participants who had received two doses of vaccine or placebo. Serious adverse events were assessed in all participants who had received at least one dose. The median follow-up time was 48 days after the first dose (interquartile range, 39–58 days).
Results:
A total of 21,977 adults were randomly assigned to the vaccine (n = 16,501) or placebo group (n = 5,476); 19,866 received two doses of vaccine or placebo and were included in the primary outcome analysis. There was no significant difference in age, sex, and comorbidity distribution between both groups. By the time the database was locked (median 48 days after first dose), 16 (0.1%) of 14,964 participants in the vaccine group and 62 (1.3%) of 4,902 in the placebo group were confirmed to have COVID-19; vaccine efficacy was 91.6% (95% confidence interval, 85.6–95.2). Any time after dose 1, 79 (0.5%) in the vaccine group and 96 (1.8%) in the placebo group had COVID-19, translating to a 73.1% efficacy. The difference between vaccine and placebo was noted approximately 16-18 days after dose 1. There were no cases of moderate to severe COVID-19 in the vaccine group, and 20 cases in the placebo group. Overall efficacy was similar across prespecified subgroups. Immunogenicity analyses at 42 days post-vaccine showed robust neutralizing antibody production in the vaccine group, with a stronger response in the younger age group (18-30 years).
There was no difference in serious adverse events between the vaccine group (45 [0.3%]) and placebo group (23 [0.4%]). Four deaths were reported during the study (three [<0.1%] of 16,427 participants in the vaccine group and one [<0.1%] of 5,435 participants in the placebo group), none of which were considered related to the vaccine.
Conclusions:
Gam-COVID-Vac was 91.6% effective in preventing COVID-19 at 21 days after the initial dose and was well tolerated in those who received both doses.
Perspective:
The landscape of vaccines effective against SARS-CoV-2 continues to widen. Gam-COVID-Vac now joins mRNA-based and other adenoviral-based vaccines with promising phase 3 interim analyses. One concern of adenoviral vectors for vaccine is their induction of immune response against vector components rather than the antigen. Gam-COVID-Vac minimizes this effect using two different vectors. Gam-COVID-Vac has been approved for storage at 2-8°C (although the liquid form was used in the study, requiring -18°C storage temperature). While the follow-up time of the study was short (median of 48 days), efficacy was apparent 18 days after the initial dose, and homogenous across age groups, sex, and burden of comorbidities. The study included over 2,000 participants aged >60 years and showed robust immune response in that age group with equivalent efficacy. Gam-COVID-Vac is already released in Russia for public use.
Clinical Topics: COVID-19 Hub, Prevention
Keywords: Adenoviridae, Antibodies, Neutralizing, Coronavirus, COVID-19, Disease Vectors, Glycoproteins, Immunity, Immunoglobulin G, Immunoglobulin M, Polymerase Chain Reaction, Primary Prevention, Vaccination, Vaccines
< Back to Listings
