Sputnik-V reactogenicity and immunogenicity in the blood and mucosa: a prospective cohort study

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.

Comparing the Safety and Immunogenicity of homologous (Sputnik V) and heterologous (BNT162B2) COVID-19 prime-boost vaccination

“…Firstly, from our assessment of reactogenicity, we observed overall low severity of adverse events in both trial arms, with local injection site being the most common adverse event. This result is comparable to adverse events documented in other reports comparing homologous and heterologous boosting (9,13,(17)(18)(19), and each vaccine independently (20,21). The incidence of adverse events was consistently higher in those aged <40 years, which is a common trend in SARS-CoV-2 vaccination studies (20,22).…”

Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated

“…AZD1222 vaccinees who experienced breakthrough infections displayed robust anamnestic IgG responses, which correlated with reduced viral loads and durations of viral shedding in saliva. Although we and others have observed transient increases in NELF IgA levels from vaccinees with prior SARS-CoV-2 infection (22,41,43), intramuscular vaccination with adenovirus-and mRNA-based COVID-19 vaccines does not appear to induce anamnestic NELF IgA responses in SARS-CoV-2-seronegative vaccinees despite eliciting IgA responses in serum (43)(44)(45). These findings suggest that different approaches (e.g., use of adjuvants, other delivery routes) will be required to improve mucosal immunogenicity for currently licensed COVID-19 vaccines (46).…”

COVID-19 Vaccination and Lethality Reduction: A Prospective Cohort Study in Venezuela

“…Our study revealed a higher prevalence of previous COVID-19 infections among vaccinated individuals when compared to the unvaccinated ones. One potential hypothesis for this observation could be the risk of breakthrough infections following vaccination, particularly noted with inactivated whole virus vaccines such as BBIBP-CorV [40,41] and Gam-COVID-Vac [42]. Additionally, vaccine hesitancy, often accompanied by a denial of the virus's existence or the severity of the disease, may contribute to underreporting of infection rates within the unvaccinated population [43].…”