Unraveling the humoral immune response following a SARS-CoV-2 infection and vaccination

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus infectious disease 2019 (COVID-19). SARS-CoV-2 caused a pandemic from 2020 to 2023, which has had a profound impact on healthcare systems, economies, and general well-being of people around the world. This thesis focuses on the humoral immune response following SARS-CoV-2 infection and vaccination. First, we studied the immune response following a primary SARS-CoV-2 wild-type or variant of concern (VOC) infection. We observed that in general SARS-CoV-2 is immunogenic, but each VOC elicited distinct humoral immune responses. Using antigenic cartography, we revealed that Omicron is antigenically distinct from earlier VOCs. Fortunately, although antibody cross-neutralization between VOCs was reduced, antibody Fc-mediated effector functions and memory B cell responses were broader. Next, we compared this antibody response post-infection with that following vaccination. In addition, we studied the differences in immune responses elicited by various COVID-19 vaccines used in the Netherlands, and observed a superior antibody response elicited by mRNA vaccines. Additionally, to prepare for future human coronavirus (hCoV) outbreaks, we studied the antibody cross-reactivity of convalescent SARS-CoV-2 and post-vaccination sera against other hCoVs. We observed that most cross-reactive antibodies targeted the S2 subdomain of the spike protein, identifying the S2 subdomain as a promising substrate for a pan-coronavirus vaccine. Together, these findings contributed to the understanding of the humoral immune response following SARS-CoV-2 infection and vaccination, informed national healthcare policies, and may guide future research on COVID-19 and other infectious diseases.