Ad5-nCoV boosted vaccine and reinfection-induced memory T/B cell responses and humoral immunity to SARS-CoV-2: based on two prospective cohorts

Abstract

Here, we regularly followed SARS-CoV-2 infected cohorts to investigate the combined effects of neutralizing antibodies (NAbs) and B and T cell profiles during the convalescent period. Ten participants infected with SARS-CoV-2 in December 2022 were selected to assess the effects of an inhaled adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV) booster on B cells and humoral immunity. To evaluate T cell responses, eight primary and 20 reinfection participants were included. Blood samples from all 38 participants were collected at 1-, 2-, and 6-months post-infection. The assays included single B cell technology, activation-induced marker (AIM) assays, and pseudovirus neutralization. In the first cohort, eighteen monoclonal antibodies (mAbs) with neutralizing activity from memory B cells (MBC) against SARS-CoV-2 mutants were obtained by high throughput single-B-cell cloning method, which lasted from 1- month to 6- month post infection. The overall number of mAbs from MBC in the inhaled Ad5-nCoV-boosted immunization group was higher than that in the non-boosted immunization group at 2-, and 6-months post-infection. In the second cohort, circulating T follicular helper cells (cTfh) and AIM + CD4 + T cells increased over time in the reinfection group (P < 0.05). The serum NAb levels against XBB.1.22, EG.5.1, and JN.1 in the primary infection group tended to increase from the post 1-month to 2-month infection (P < 0.05). In both cohorts, serum NAb titers showed significant immune escape, while cTfh and AIM + CD4 + T cells in the second cohort essentially showed no immune escape to new strains (including XBB, EG.5) during the six-month follow-up period. AIM + CD4 + T cells against BA.5 and EG.5 were strongly negatively correlated with the time to viral clearance in the reinfected group after months of 6M infection. The broader significance of this study was to comprehensively assess the ability of the SARS-CoV-2 boosted immunization and reinfection-induced generation of T/B cell immune memories in preventing reinfection.