Abstract
Background: Durable vaccine-mediated immunity relies on the generation of long-lived plasma cells and memory B cells (MBCs), differentiating upon germinal center (GC) reactions. SARS-CoV-2 mRNA vaccination induces a strong GC response in healthy volunteers (HC), but limited data is available about response longevity upon rituximab treatment.
Methods: We evaluated humoral and cellular responses upon 3rd vaccination in seven patients with rheumatoid arthritis (RA) who initially mounted anti-spike SARS-CoV-2 IgG antibodies after primary 2x vaccination and got re-exposed to rituximab (RTX) 1-2 months after the second vaccination. Ten patients with RA on other therapies and ten HC represented the control groups. As control for known long-lived induced immunity, we analyzed humoral and cellular tetanus toxoid (TT) immune responses in steady-state.
Results: After 3 rd vaccination, 5/7 seroconverted RTX patients revealed lower anti-SARS-CoV-2 IgG levels but similar neutralizing capacity compared with HC. Antibody levels after 3rd vaccination correlated with values after 2nd vaccination. Despite significant reduction of circulating total and antigen-specific B cells in RTX re-exposed patients, we observed the induction of IgG+ MBCs upon 3 rd vaccination. Notably, only RTX treated patients revealed a high amount of IgA+ MBCs before and IgA+ plasmablasts after 3 rd vaccination. IgA+ B cells were not part of the steady state TT+ B cell pool. TNF-secretion and generation of effector memory CD4 spike-specific T cells were significantly boosted upon 3 rd vaccination.
Summary: On the basis of pre-existing affinity matured MBCs within primary immunisation, RTX re-exposed patients revealed a persistent but atypical GC immune response accompanied by boosted spike-specific memory CD4 T cells upon SARS-CoV-2 recall vaccination.
Keywords: SARS-CoV-2; germinal center (GC); memory B cell (MBC); rituximab (RTX); vaccination.
【저자키워드】 SARS-CoV-2, vaccination., memory B cell (MBC), germinal center (GC), rituximab (RTX), 【초록키워드】 Treatment, mRNA vaccination, immune response, vaccination, therapy, Immunity, CD4, rheumatoid arthritis, memory, B cell, anti-SARS-CoV-2 IgG, SARS-CoV-2 IgG antibody, Patient, neutralizing capacity, recall, patients, Anti-spike, memory B cell, antibody level, MBC, cellular response, cellular, Atypical, humoral, CD4 T cell, reduction, Steady state, Reactions, second vaccination, control groups, plasmablast, circulating, effector memory, Cell, memory B, Seven, vaccine-mediated immunity, analyzed, significantly, evaluated, seroconverted, correlated, induce, accompanied, antigen-specific B cell, healthy volunteer, long-lived plasma cell, mounted, RTX, spike-specific T cell, treated patient, 【제목키워드】 persistent, SARS-CoV-2 vaccination, Atypical,