Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

Lederer, K.; Parvathaneni, K.; Painter, M. M.; Bettini, E.; Agarwal, D.; Lundgreen, K. A.; Weirick, M.; Goel, R. R.; Xu, X.; Drapeau, E. M.; Gouma, S.; Greenplate, A. R.; Le Coz, C.; Romberg, N.; Jones, L.; Rosen, M.; Besharatian, B.; Kaminiski, M.; Weiskopf, D.; Sette, A.; Hensley, S. E.; Bates, P.; Wherry, E. J.; Naji, A.; Bhoj, V.; Locci, M.

Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. In this study, through a fine-needle-aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant (KTX) recipients. We found that, unlike healthy subjects, KTX recipients presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cells, SARS-CoV-2 receptor-binding-domain-specific memory B cells and neutralizing antibodies. KTX recipients also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals, and suggest a GC-origin for certain humoral and memory B cell responses following mRNA vaccination.