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

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

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Although 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 immunoglobulin (Ig)A+ subset and secondary MBCs that are mostly IgG+ and cross-react with 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 do 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.

Original languageEnglish (US)
Article number109823
JournalCell reports
Volume37
Issue number2
DOIs
StatePublished - Oct 12 2021

Bibliographical note

Funding Information:
The authors acknowledge Jennifer Walter and Charles Elwood for technical help and maintenance of mice. We also acknowledge the contributions of the University of Minnesota Clinical Translational Science Institute (CTSI) in the start-up of this study, including Carrie McKenzie, Francoise Mercadier-Crevel, and Sydney Viel. This work was supported by a special grant from the Office of the Dean of the University of Minnesota Medical School . Partial funding for the clinical efforts was provided by the non-profit organization Achieving Cures Together .

Funding Information:
The authors acknowledge Jennifer Walter and Charles Elwood for technical help and maintenance of mice. We also acknowledge the contributions of the University of Minnesota Clinical Translational Science Institute (CTSI) in the start-up of this study, including Carrie McKenzie, Francoise Mercadier-Crevel, and Sydney Viel. This work was supported by a special grant from the Office of the Dean of the University of Minnesota Medical School. Partial funding for the clinical efforts was provided by the non-profit organization Achieving Cures Together. Conceptualization, K.A.P. and M.K.J.; methodology, K.A.P.; formal analysis, K.A.P. and M.K.J.; investigation, all authors; writing ? original draft, M.K.J. and K.A.P.; writing ? review & editing, all authors; visualization, M.K.J.; funding acquisition, M.K.J. and A.K.; supervision, M.K.J.; IRB protocol development, A.K.; clinical team supervision, A.J.K. A.K. and J.R.; participant recruitment, consent, clinical metadata capture, A.J.K. D.K. R.B. C.G. C.E. A.K. B.P.V. M.M. and E.S.; sample processing, C.E. and S.L. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects.

Publisher Copyright:
© 2021 The Authors

Keywords

  • SARS-CoV-2
  • atypical memory B cell
  • mRNA vaccine
  • memory B cell
  • plasmablast

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