High affinity memory B cells induced by SARS-CoV-2 infection produce more plasmablasts and atypical memory B cells than those primed by mRNA vaccines

Pape, Kathryn A.; Dileepan, Thamotharampillai; Kabage, Amanda J.; Kozysa, Daria; Batres, Rodolfo; Evert, Clayton; Matson, Michael; Lopez, Sharon; Krueger, Peter D.; Graiziger, Carolyn; Vaughn, Byron P.; Shmidt, Eugenia; Rhein, Joshua; Schacker, Timothy W.; Khoruts, Alexander; Jenkins, Marc K.

While both infections and vaccines induce memory B cell (MBC) populations that participate in secondary immune responses, the MBCs generated in each case can differ. Here we compare SARS-CoV-2 spike receptor binding domain (S1-RBD)-specific primary MBCs that form in response to infection or a single mRNA vaccination. Both primary MBC populations have similar frequencies in the blood, and respond to a second S1-RBD exposure by rapidly producing plasmablasts with an abundant IgA+ subset, and secondary MBCs that are mostly IgG+ and cross-react on the B.1.351 variant. However, infection-induced primary MBCs have better antigen-binding capacity and generate more plasmablasts and secondary MBCs of the classical and atypical subsets than vaccine-induced primary MBCs. Our results suggest that infection-induced primary MBCs have undergone more affinity maturation than vaccine-induced primary MBCs and produce more robust secondary responses.