SARS-CoV-2-specific memory B cell responses are maintained after recovery from natural infection and post vaccination

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has resulted in major worldwide disruption and loss of life over the last 2 years. Many research studies have shown waning serological SARS-CoV-2-specific IgG antibody titers over time, yet, it is unclear whether these changes are reflected in the potential functional reactivation of SARS-CoV-2 antigen-specific memory B cells (MBC) populations. This is especially true in the contexts of differing COVID-19 disease severity and after vaccination regimens. This study aimed to investigate these by polyclonal in vitro reactivation of MBC populations followed by analysis using SAR-CoV-2 antigen-specific B cell ELISpots and IgG antibody ELISAs. Natural disease-associated differences were investigated in 52 donors who have recovered from COVID-19 with varying disease severity, from asymptomatic to severe COVID-19 disease, accompanied by a longitudinal evaluation in a subset of donors. Overall, these data showed limited disease severity-associated differences between donor groups but did show that COVID-19 serologically positive donors had strong antigen-specific MBC-associated responses. MBC responses were better maintained 6 months after recovery from infection when compared to serological antigen-specific IgG antibody titers. A similar investigation after vaccination using 14 donors showed robust serological antigen-specific antibody responses against spike protein that waned over time. MBC-associated responses against spike protein were also observed but showed less waning over time, indicating maintenance of a protective response 6 months after vaccination. Further research is required to evaluate these putatively functional SARS-CoV-2-specific responses in the context of long-term protection mediated by vaccination against this pathogen.