Abstract
Background: Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-19 vaccine now used in >70 countries. Yet there is a shortage of data on this vaccine's performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in a multi-ethnic cohort from Kazakhstan. Methods: COVID-19-free participants (n=82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays.
Findings: Of the 73 and 70 participants retained post-dose 1 and 2, respectively, most (>50%) reported mild-to-moderate injection site or systemic reactions to vaccination; no severe or potentially life-threatening conditions were reported. dose 1 appeared to be more reactogenic than dose 2, with fatigue and headache more frequent in participants with prior COVID-19 exposure. After dose 2 nausea was more common in subjects without prior COVID-19. The combined S-IgG and S-IgA seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization titers was 83% post-dose 1', and increased to 98% post-dose 2', with the largest relative increase observed in participants without prior COVID-19 exposure. Nasal S-IgG and S-IgA increased post-dose 1, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count.
Interpretation: Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal, suggesting that adjustments to the current vaccine dosing regimen may be necessary to optimize immunization efficacy and cost-effectiveness. Although Sputnik-V appears to have a reactogenicity profile similar to that of other COVID-19 vaccines, the observed alterations to the GRO/platelet axis call for further investigation of Sputnik V effects on systemic immunology.
Funding: Ministry of Education and Science of the Republic of Kazakhstan.
Research in context
Evidence before this study: We searched PubMed, bioRxiv and medRxiv and quieried the "COVID-19 Research Explorer" application on 13 January 2022 for primary research articles describing the reactogenicity and immunogenicity of the Sputnik-V/Gam-Cov vaccine with no restriction for language or date of publication. Our search terms included "Sputnik-V", "Sputnik", "Gam-COVID-Vac", “Safety” “Adverse events”, “Immunogenicity”, “Immunology”. We found 16 publications, 9 of which have been peer-reviewed. Five of the studies (from Argentina, Bosnia and Herzegovina, Iran, Russia and Serbia) assessed both the safety/adverse events and immunogenicity associated with Sputnik-V. Three studies (from Argentina and San Marino) reported only the safety and/or side effects, eight studies (from Argentina, Iran, Pakistan, Russia, Sri Lanka, Venezuela) assessed only the immunogenicity of Sputnik-V. One study presented serum cytokine data from vaccinees at days 21 and 42 post-vaccination; however the authors did not provide sufficient detail on the methodology of this analysis and their findings appeared to contradict the results of a similar analysis of Pfizer/BioNtech-elicited cytokine changes. Only three of the immunogenicity studies (from Argentina and Venezuela) accounted for prior COVID-19 exposure. We did not find any studies detailing nasal mucosal immune responses elicited by Sputnik-V. In summary, Sputnik-V was found to be safe, eliciting strong humoral immune responses sustained at high levels for up to 90 days post-vaccination; while two studies reported no evident benefit of dose 2 on Spike or RBD IgG titres in subjects with prior COVID-19 history, one study found dose 2 to be beneficial at boosting RBD IgG titres in all participants regardless of prior COVID-19 exposure.
Added value of this study: In this prospective, cohort study, we report both safety and adverse event frequency and immunologic findings for subjects, who received one (n=73) or two doses (n=70) of Sputnik-V in Kazakhstan. Sputnik-V in this cohort has a reactogenicity profile similar to that reported earlier for other cohorts. The vaccine induces a robust immune response in both blood and mucosa. While dose 1 boosted both blood and mucosal SARS-CoV-2 immunity, the effects of dose 2 were minimal and limited to participants without prior COVID-19 exposure. Sputnik-V elicited a sustained reduction of systemic growth regulated oncogene, and this chemokine reduction correlated with platelet count elevation.
Implications of all the available evidence: Overall these findings contribute to the growing body of evidence that Sputnik-V is a safe vaccine inducing robust systemic and mucosal immunity against SARS-CoV-2. However, these data also suggest that adjustments to the current Sputnik-V prime-boost regimen may be necessary to increase the cost effectiveness and immunization efficacy of Sputnik-V, given the limited benefit provided by the second Sputnik-V dose. Further investigation of Sputnik V effects on systemic immunology is also warranted.