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

Here, we regularly followed two 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 infected participants 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 in the first cohort. To evaluate T cell responses, eight primary and 20 reinfection participants were included in the second cohort. Blood samples from all 38 participants were collected at 1-, 2-, and 6-months post-infection. 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 boosted immunization group was higher than that in the nonboosted 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 (<i>P</i> &lt; 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). AIM ⁺CD4 ⁺T cells against BA.5 and EG.5 were strongly negatively correlated with the time to viral clearance in the reinfected group at 6-months post-infection. We comprehensively assessed the ability of the SARS-CoV-2 boosted immunization and reinfection-induced generation of T/B cell immune memories in preventing reinfection.