Functional Profiling of In Vitro Reactivated Memory B Cells Following Natural SARS-CoV-2 Infection and Gam-COVID-Vac Vaccination

Abstract

Both SARS-CoV-2 infection and vaccination have previously been demonstrated to elicit robust, yet somewhat limited immunity against the evolving variants of SARS-CoV-2. Nevertheless, reports performing side-by-side comparison of immune responses following infection vs. vaccination have been relatively scarce. The aim of this study was to compare B-cell response to adenovirus-vectored vaccination in SARS-CoV-2-naive individuals with that observed in the COVID-19 convalescent patients six months after the first encounter with the viral antigens. We set out to use a single analytical platform and performed comprehensive analysis of serum levels of receptor binding domain (RBD)-specific and virus-neutralizing antibodies, frequencies of RBD-binding circulating memory B cells (MBCs), MBC-derived antibody-secreting cells, as well as RBD-specific and virus-neutralizing activity of MBC-derived antibodies after Gam-COVID-Vac (Sputnik V) vaccination and/or natural SARS-CoV-2 infection. Overall, natural immunity was superior to Gam-COVID-Vac vaccination. The levels of neutralizing MBC-derived antibodies in the convalescent patients turned out to be significantly higher than those found following vaccination. Our results suggest that after six months, SARS-CoV-2-specific MBC immunity is more robust in COVID-19 convalescent patients than in Gam-COVID-Vac recipients. Collectively, our data unambiguously indicate that natural immunity outperforms Gam-COVID-Vac-induced immunity six months following recovery/vaccination, which should inform healthcare and vaccination decisions.

Hybrid Immunity from Gam-COVID-Vac Vaccination and Natural SARS-CoV-2 Infection Confers Broader Neutralizing Activity against Omicron Lineage VOCs Than Revaccination or Reinfection

“…Interestingly, we show here that hybrid immunity is more effective than immunity induced by two natural infections. These results contradict some other data that suggest the advantages of the immune response induced by natural infection compared to the immune response to vaccine immunogens [ 18 , 24 , 25 , 26 ]. There may be several explanations.…”

“…This vaccine belongs to the first generation of COVID-19 vaccines and is based on the use of the “wild-type” Spike protein of SARS-CoV-2 encoded by two replication-incompetent adenovirus vectors (rAd26 and rAd5) [ 17 ]. Previously, it was found that GAM-COVID-Vac induced a broader immune response in convalescents compared to naive recipients [ 18 , 19 ]. In the present study, we set out to examine individuals from four groups of donors: those who were booster vaccinated, those who were twice infected but never vaccinated, those who were infected after vaccination, and those who were vaccinated following SARS-CoV-2 infection.…”

Antigenic Cartography Indicates That the Omicron BA.1 and BA.4/BA.5 Variants Remain Antigenically Distant to Ancestral SARS-CoV-2 after Sputnik V Vaccination Followed by Homologous (Sputnik V) or Heterologous (Comirnaty) Revaccination

“…Specifically, these spike variants had the following substitutions: Δ69–70, Δ144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H (Alpha); L18F, D80A, D215G, Δ241–243, R246I, K417N, E484K, N501Y, D614G, A701V (Beta); T19R, G142D, Δ156–157, R158G, L452R, T478K, D614G, P681R, D950N (Delta); A67V, Δ69–70, T95I, G142D, Δ143–145, Δ211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F (Omicron BA.1); T19I, Δ24–26, A27S, Δ69–70, G142D, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K (Omicron BA.4/BA.5). Lentiviral particles were pseudotyped with the SARS-CoV-2 spike protein from either the WT strain or the variant strains as previously described [ 30 ]. Pseudoviral particles were frozen at −70 °C for later use in neutralization assays.…”

Class switch towards spike protein-specific IgG4 antibodies after SARS-CoV-2 mRNA vaccination depends on prior infection history

“…Similar results were found for the spike-specific antibody response; previously infected individuals reached similar specific antibody levels after their first vaccination as non-infected individuals after their second dose of vaccine 5 . After vector-based vaccinations, the level of neutralizing memory B cell-derived antibodies appeared to be significantly lower in Sputnik recipients than in COVID-19 convalescent patients 6 . Besides this, different quantities and quality of CD4+ T cell, CD8+ T cell, and antibody responses were induced by mRNA-based (Moderna and Pfizer-BioNTech), vector-based (Janssen), and protein-based vaccines (Novavax).…”