Pre-existing humoral immunity to human common cold coronaviruses negatively impacts the protective SARS-CoV-2 antibody response
Chun-Yang Lin, Joshua Wolf, David C. Brice, Yilun Sun, Macauley Locke, Sean Cherry, Ashley Castellaw, Marie Wehenkel, Jeremy Chase Crawford, Veronika I. Zarnitsyna, Daniel Luque Duque, Kim Allison, E. Kaitlynn Allen, Scott A. Brown, Alexandra H. Mandarano, Jeremie H. Estepp, Aditya H. Gaur, James M. Hoffman, Tomi Mori, Elaine Tuomanen, Richard J. Webby, Hana Hakim, Randall T. Hayden, Diego R. Hijano, Walid Awad, Resha Bajracharya, Brandi L. Clark, Valerie Cortez, Ronald H. Dallas, Thomas Fabrizio, Pamela Freiden, Ashleigh Gowen, Jason Hodges, Allison M. Kirk, Ericka Kirkpatrick Roubidoux, Robert C. Mettelman, Jamie Russell-Bell, Aisha Souquette, James Sparks, Lee-Ann Van de Velde, Ana Vazquez-Pagan, Kendall Whitt, Taylor L. Wilson, David E. Wittman, Nicholas Wohlgemuth, Gang Wu, Charles Taylor, Carmen Molina-Parı́s, Stacey Schultz‐Cherry, Li Tang, Paul G. Thomas, Maureen A. McGargill
Abstract
SARS-CoV-2 infection causes diverse outcomes ranging from asymptomatic infection to respiratory distress and death. A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoVs) impacts susceptibility to SARS-CoV-2 infection or immunity following infection and vaccination. Therefore, we analyzed samples from the same individuals before and after SARS-CoV-2 infection or vaccination. We found hCCCoV antibody levels increase after SARS-CoV-2 exposure, demonstrating cross-reactivity. However, a case-control study indicates that baseline hCCCoV antibody levels are not associated with protection against SARS-CoV-2 infection. Rather, higher magnitudes of pre-existing betacoronavirus antibodies correlate with more SARS-CoV-2 antibodies following infection, an indicator of greater disease severity. Additionally, immunization with hCCCoV spike proteins before SARS-CoV-2 immunization impedes the generation of SARS-CoV-2-neutralizing antibodies in mice. Together, these data suggest that pre-existing hCCCoV antibodies hinder SARS-CoV-2 antibody-based immunity following infection and provide insight on how pre-existing coronavirus immunity impacts SARS-CoV-2 infection, which is critical considering emerging variants.