Imprinting of B cells in SARS-CoV-2 prototype strain infection compared to AZD1222 (ChAdOx nCoV-19) vaccination

Understanding the behavior of B cell subsets in infections and vaccination is important to determine how protective humoral immunity is established. Here, we performed a cross-sectional study and evaluated subjects who were either acutely infected with SARS-CoV-2, recovered from COVID-19, or received two doses of the AZD1222 vaccine. PBMC collected from these subjects were subjected to in vitro stimulation with R848 + rIL-2 to promote terminal differentiation of B cells into antibody-secreting cells (ASC), and the abundance of pan (irrespective of antigen specificity) and SARS-CoV-2 Spike S1 domain-reactive IgG + ASC were evaluated using the ELISPOT method. Stimulated PBMCs were recovered from ELISPOT assays and further characterized using multiparametric flow cytometry. Moreover, culture supernatants from the ELISPOT assay were assessed for soluble B cell activating factors (BAFF, APRIL, and CD40L). Lastly, using a commercial ELISA kit, the abundance of IgA and IgG in plasma with specificity for the Spike 1 domain was evaluated in the groups. We showed that most recovered individuals display a robust Spike 1-specific ASC response compared to acute COVID-19 and those vaccinated. Although the frequency of total B cells or B-cell subsets did not vary when comparing the four groups, plasmablasts are commonly increased for naïve and double negative B-cells in the acute, recovered, and vaccinated groups. Considering the IgA and IgG production profile, similar IgA and IgG production appears to be present in acute and recovered patients. During vaccination, more IgG is produced than IgA. This could be due to the increased frequency of IgG + plasmablasts and IgG + memory B cells in acute cases and IgG + memory B cells in vaccinated patients. Furthermore, in acute patients, BAFF quantities were positively correlated with total B cells and IgG + plasmablasts but negatively correlated with IgA + plasmablasts. Our data suggest that vaccination and natural infection in COVID-19 induce a differential profile and functionality of B cells. Therefore, we recommend that new vaccines against COVID-19 incorporate molecular adjuvants that regulate B lymphocyte functionality, that they are more effective in inducing an ACS IgG + response to SARS-CoV-2 antigens and, consider the beneficial aspects of the IgA response in addition to the IgG.