Abstract
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.
Highlights
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh member of the human coronaviruses
Reactivity of circulating serum IgG was measured by ELISA with a panel of SARS-CoV-2 antigens that include full-length S ectodomain, receptor-binding domain (RBD), S2-only ectodomain subunit, and N proteins
We offer the following key findings: (i) the increase in the coronavirus-reactive IgG binding avidity in both serum and memory B cells (MBCs) compartments, (ii) the unique signature of the N-reactive response, (iii) the broad coronavirus-reactive IgG PB response during acute phase indicating the activation of pre-existing cross-reactive MBCs, and (iv) the rapid formation of S2-reactive IgG MBCs following infection
Summary
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh member of the human coronaviruses. It belongs to the genus β-coronavirus, together with the highly lethal SARS-CoV (2003) and middle east respiratory syndrome (MERS) CoV, as well as the seasonal common cold human coronavirus (HCoV) OC43 and HKU1. The profile of immune response following seasonal coronavirus infection had not received much attention, with recent reports indicating that the immunity against human coronaviruses is either short-lived or the viruses evolve to escape immune pressure [1,2]. SARS-CoV-2 infection generates a strong circulating Abs response against the surface spike (S) glycoprotein and the internal nucleocapsid (N) protein [6,7,8,9]. Abs reactive to the membrane-distal S1 subunit of S protein, against the N-terminal domain (NTD) and receptor-binding domain (RBD), are known to neutralize the virus [11,12,13,14]
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