Coronavirus Immune History Affects Breadth of Anti-SARS-CoV-2 Receptor-Binding Domain Responses.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B924
Abstract ID: 5629

Presenting Author:
David C Brice , Postdoctoral Research Associate at St. Jude Children’s Res. Hosp.

Abstract:

As novel SARS-CoV-2 variants continue to emerge, it is essential to gain further insight into the impact of imprinting on the protective antibody response to SARS-CoV-2. Utilizing a longitudinal cohort with samples collected before and after infection or vaccination, we assessed associations between pre-existing humoral immunity to common cold human coronaviruses (hCoVs) and the subsequent antibody response to the Spike Receptor Binding Domain (RBD) of different variants of SARS-CoV-2 following infection and vaccination. We found baseline anti-hCoV Spike IgM levels negatively correlate with anti-RBD breadth after infection, but not vaccination, with binding to the RBDs more antigenically distant to the Wuhan strain most affected. To investigate the effect of prior exposure to Spike proteins of individual coronaviruses, we utilized a mouse model. Unexpectedly, initial vaccination with SARS-CoV-1 Spike generated higher levels of SARS-CoV-2 RBD-specific antibodies compared to initial immunization with SARS-CoV-2 Spike, a phenomenon that continued even after SARS-CoV-2 Spike boosting of both groups. Moreover, SARS-CoV-1 Spike vaccination induced a broader and more durable SARS-CoV-2 RBD antibody response compared to SARS-CoV-2 Spike vaccination. Overall, these data highlight the lasting impact of prior exposure to related coronaviruses and demonstrate how SARS-CoV-1 Spike exposure induces a broader antibody response to the RBD of SARS-CoV-2 variants compared to SARS-CoV-2 Spike.