Comparative Analysis of SARS-CoV-2-Specific B Cell and Humoral Responses Elicited by Sputnik V in Naïve and COVID-19-Recovered Vaccine Recipients

Background: The development of effective vaccines against SARS-CoV-2 remains a global health priority. Despite extensive use, several key immunological features of Sputnik V, an adenovirus-based two-component vaccine against SARS-CoV-2, need to be explored in detail. These include the effects of Sputnik V on B cell immunity and its ability to elicit antibody responses that are active against emerging neutralization-resistant SARS-CoV-2 variants.   Methods: Our study included a cohort of 22 volunteers who received complete Sputnik V vaccination (two doses 21 days apart), 5 of who had a recent history of mild COVID-19, and 17 constituted a group of SARS-CoV-2 unexposed individuals. The frequencies of receptor-binding domain (RBD)-specific plasmablasts and B memory cells (MBCs), circulating and MBC-derived antibody secreting cells, virus binding, and virus-neutralizing activities of the sera, as well as samples of MBC-derived antibodies were analyzed using flow cytometry, ELISA, enzyme-linked immunosorbent spot (ELISpot), and pseudotyped virus neutralization assay at four time points spanning the period immediately before, during, and after vaccination.  Findings: Longitudinal analysis of circulating serum antibodies showed that the anti-RBD IgG levels in naive vaccine recipients substantially increased after the second vaccine dose (P<0.001), while in COVID-19-recovered individuals, this typically occurred after the first dose (P=0.0084).  In recovered vaccine recipients, RBD-specific MBCs and SARS-CoV-2-specific MBC-derived antibody-secreting cells (ASCs) were already present prior to vaccination and remained stable until day 85. However, in naive vaccine recipients, RBD-specific MBCs and MBC-derived ASCs became detectable after the second dose and by day 85, they reached the levels observed in recovered vaccine recipients.  In vitro stimulated MBCs from recovered individuals secreted a significant amount of anti-RBD IgG both on days 28 and 85. These antibodies demonstrated robust neutralization of the Wuhan Spike-pseudotyped lentivirus. In the naive group, the level of anti-RBD IgG secretion was five- to six-fold reduced compared to that of the recovered group (P<0.001), and maximum virus neutralization (Wuhan spike) was achieved only on day 85. At this time point, the sera from both naive and recovered vaccine recipients displayed neutralizing activities against the ancestral Wuhan and B.1.351 viruses, albeit the magnitude of neutralization against the mutant variant was 5.1–5.3-fold lower.  Interpretation: B cell and antibody responses to Sputnik V were heavily dependent on whether the vaccinee had a history of SARS-CoV-2 infection or not. All the recovered and most naive Sputnik V recipients displayed neutralizing antibody responses against the ancestral Wuhan and B.1.351 viruses. Plasmablast, RBD-specific MBCs, SARS-CoV-2-specific MBC-derived ASC responses, and humoral responses were more prominent in the recovered group of vaccinees than in the naive subgroup, which may be indicative of their higher degree of long-term protection.  Funding: This work was supported by the Russian Science Foundation (Project 21-15-00331) and the Russian Fund for Basic Research (20-04-60527). Declaration of Interest: None to declare. Ethical Approval: The study protocol was reviewed and approved by the Medical Ethical Committee of Institute of Immunology (#12-1, December 29, 2020).