Formation and Expansion of Memory B Cells against Coronavirus in Acutely Infected COVID-19 Individuals
A. Karim Embong,
Phuong Nguyen-Contant,
Jiong Wang,
Preshetha Kanagaiah,
Francisco A. Chaves,
Theresa F. Fitzgerald,
Qian Zhou,
Gabrielle Kosoy,
Angela R. Branche,
Benjamin L. Miller,
Martin S. Zand,
Mark Y. Sangster,
David J. Topham
Affiliations
A. Karim Embong
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14620, USA
Phuong Nguyen-Contant
ACM Global Laboratories, Rochester, NY 14624, USA
Jiong Wang
Division of Nephrology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14620, USA
Preshetha Kanagaiah
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14620, USA
Francisco A. Chaves
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14620, USA
Theresa F. Fitzgerald
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14620, USA
Qian Zhou
Division of Nephrology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14620, USA
Gabrielle Kosoy
Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY 14620, USA
Angela R. Branche
Department of Medicine, University of Rochester Medical Center, Rochester, NY 14620, USA
Benjamin L. Miller
Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY 14620, USA
Martin S. Zand
Division of Nephrology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14620, USA
Mark Y. Sangster
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14620, USA
David J. Topham
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14620, USA
Infection with the β-coronavirus SARS-CoV-2 typically generates strong virus-specific antibody production. Antibody responses against novel features of SARS-CoV-2 proteins require naïve B cell activation, but there is a growing appreciation that conserved regions are recognized by pre-existing memory B cells (MBCs) generated by endemic coronaviruses. The current study investigated the role of pre-existing cross-reactive coronavirus memory in the antibody response to the viral spike (S) and nucleocapsid (N) proteins following SARS-CoV-2 infection. The breadth of reactivity of circulating antibodies, plasmablasts, and MBCs was analyzed. Acutely infected subjects generated strong IgG responses to the S protein, including the novel receptor binding domain, the conserved S2 region, and to the N protein. The response included reactivity to the S of endemic β-coronaviruses and, interestingly, to the N of an endemic α-coronavirus. Both mild and severe infection expanded IgG MBC populations reactive to the S of SARS-CoV-2 and endemic β-coronaviruses. Avidity of S-reactive IgG antibodies and MBCs increased after infection. Overall, findings indicate that the response to the S and N of SARS-CoV-2 involves pre-existing MBC activation and adaptation to novel features of the proteins, along with the potential of imprinting to shape the response to SARS-CoV-2 infection.
