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

Abstract

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 naïve vaccine recipients substantially increased after the second vaccine dose (PP=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 naïve group, the level of anti-RBD IgG secretion was five- to six-fold reduced compared to that of the recovered group (PInterpretation: 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 naïve 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 naïve 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).