We have investigated the immune responses of the first dose (rAd26-S) of the Gam-COVID-Vac, which is also known as Sputnik light, in a Sri Lankan population, 4 weeks after receiving the first dose and compared the immune responses with our previously published data following AZD1222, which is another adenovirus vector vaccine. The first dose of Gam-COVID-19 vaccine was shown to induce an overall seroconversion rate of 88.7%, with significantly lower seroconversion rates (81.8%) and SARS-CoV-2 specific antibody levels in individuals over 60 years of age. It induced ACE2-receptor blocking antibodies in 82.6% of individuals and the levels were significantly lower than levels seen following a single dose of AZD1222 and those following natural infection. Therefore, the overall antibody responses following a single dose of Gam-COVID-Vac appear to be significantly lower than those following a single dose of AZD1222, especially in older individuals in a Sri Lankan population13.
In the phase 1/2 studies, it was shown that the vaccine only induced neutralizing antibodies (Nabs) in 61.1% of individuals at 28 days although the antibody titres were comparable to those following natural infection6. Although the ACE2 receptor blocking antibodies are not a direct measure of Nabs, they have shown to be a surrogate indicator of Nabs15,20. Nabs have been shown to be highly predictive of protection against SARS-CoV-2 infection21, and those with lower Nabs have shown to associate with breakthrough infection in vaccinated health care workers22. Although the AZD1222 reported an efficacy rate of 76% up to 90 days following a single dose of the vaccine for the ancestral SARS-CoV-2 virus23, the efficacy of a single dose reduced to 30% for B.1.617.224. Therefore, given that the ACE2 receptor blocking antibody levels were significantly lower than following a single dose of AZD1222 and since the proportion of individuals who developed ACE2 receptor blocking antibodies were also significantly lower, especially in the older age groups, a single dose of Gam-COVID-Vac, may possibly have a reduced efficacy than AZD1222 in Sri Lanka, and so may benefit from administration of the second dose.
At the end of 4 weeks following the single dose of Gam-COVID-Vac, 81.2% had antibodies to the RBD of the WT detected by HAT, similar to levels seen following a single dose of AZD122213. However, the proportion of individuals who developed antibodies were less than those reported in the phase 1/2 study, in which 100% of the study participants developed antibodies to the RBD by 21 days6. These differences could be due to the differences in the assays used, ages of the individuals included (we had included individuals > 60 years of age), sample size (n = 18 in the published study compared to n = 69 in this study) and possible pre-existing antibodies to Ad26 reducing vaccine immunogenicity in Sri Lanka25. The lower RBD antibodies to the WT and ACE2 receptor blocking antibodies in our cohort of patients, especially in those who were > 60 years of age, in comparison to the published data, could be due to the differences in the seropositivity rates for adenovirus 26 in different age groups in different populations12. The antibody responses to the RBD of the WT, B.1.1.7 and B.1.617.2 following the first dose of Gam-COVID-Vac were similar to that of AZD1222, but significantly lower than antibody levels seen following natural infection, although antibodies to the RBD of B.1.351 were significantly higher than AZD1222. As AZD1222 was shown to have a reduced efficacy for B.1.35126, given the higher magnitude and frequency of antibodies to the RBD of B.1.351, Gam-COVID-Vac may be more effective than AZD1222 in countries, which have outbreaks due to B.1.351, although further clinical studies are required.
Although Nabs are thought to be correlated with prevention of breakthrough infections following vaccination and an important correlate of protection21, a robust T cell response is also associated with development of milder clinical disease27. Gam-COVID-Vac induced a high frequency of ex vivo IFNγ ELISpot responses to spike protein peptides in 30% of individuals, and a high frequency of CD107a producing CD4 + and CD8 + T cells along with memory B cell responses. Interestingly, both CD107a and IFNγ production was predominantly by the CD4 + T cell subset of T cells, which is similar to what was seen following a single dose of the AZD122228. However, the frequency of ex vivo IFNγ ELISpot responses and the proportion of individuals who responded to the spike protein overlapping pool of peptides was significantly lower than for AZD122213. The Gam-COVID-Vac induced ASCs, responding to S1, S2 and N recombinant proteins. Although 19/25 individuals responded to the N protein of SARS-CoV-2, these responses were of very low frequency and were several folds lower than the responses to S1 subunit. The frequency of N protein specific ASCs were also several fold lower than what we previously observed for the Sinopharm/BBIBP-CorV, which is an inactivated vaccine and therefore, induces immune responses to the N protein17. Therefore, these low frequency memory T cell responses are likely to be due to pre-existing cross reactive memory B cell responses to other seasonal coronaviruses and are unlikely to be SARS-CoV-2 specific29.
In summary, the Gam-COVID-19 first dose (rAd26-S) induced seroconversion rates in 88.7% of individuals 4 weeks following the vaccine, with significantly lower seroconversion rates in the elderly in a Sri Lankan population. ACE2 receptor blocking antibody responses were seen in 82.6% of individuals, with levels significantly lower than after a single dose of AZD1222 and following natural infection. While the antibody responses to the RBD by HAT were similar to AZD1222, the ex vivo IFNγ ELISpot responses were significantly lower. The findings suggest that the two Gam-COVID-19 doses using heterologous adenoviruses may be of particular importance in certain populations.