SARS-CoV-2 mRNA vaccine-induced immune responses in rheumatoid arthritis.

Our objective was to characterize T and B cell responses to vaccination with SARS-CoV-2 antigens in immunocompromised rheumatoid arthritis (RA) patients. In 22 RA patients, clinical and biological variables were analyzed before and 4 weeks after each of 3 messenger RNA (mRNA) vaccine doses and compared with unmatched healthy individuals. Sequentially sampled peripheral blood mononuclear cells and sera were collected to determine immune profiles and to analyze the T cell response to a spike peptide pool and B cell specificity to the receptor-binding domain (RBD). Anti-spike antibodies were detectable in 6 of 22 RA patients after 1 dose of vaccine with increasing titers after each booster dose, although the overall response was lower compared with that in healthy control individuals. Responding patients after the first dose were more likely to have RA antibodies and a higher baseline proportion of circulating follicular B cells. In RA patients, the mRNA vaccine elicited a robust CD4+ T response to a spike peptide pool following the first and second doses. Consistent with the serologies, RBD-specific B cells exhibited a modest increase after the first dose and the second dose resulted in marked increases only in a fraction of the RA patients to both ancestral and omicron RBD. Our results highlight the importance of multidose COVID-19 vaccination in RA patients to develop a protective humoral response. However, these patients rapidly develop specific T CD4+ responses, despite delayed B cell responses.