Pre-existing humoral immunity to human common cold coronaviruses negatively impacts the protective SARS-CoV-2 antibody response

• Published in: Cell host & microbe 2022-01, Vol.30 (1), p.83-96.e4
• Main Authors: Lin, Chun-Yang, Wolf, Joshua, Brice, David C., Sun, Yilun, Locke, Macauley, Cherry, Sean, Castellaw, Ashley H., Wehenkel, Marie, Crawford, Jeremy Chase, Zarnitsyna, Veronika I., Duque, Daniel, Allison, Kim J., Allen, E. Kaitlynn, Brown, Scott A., Mandarano, Alexandra H., Estepp, Jeremie H., Gaur, Aditya H., Hoffman, James M., Mori, Tomi, Tuomanen, Elaine I., Webby, Richard J., Hakim, Hana, Hayden, Randall T., Hijano, Diego R., Awad, Walid, Bajracharya, Resha, Clark, Brandi L., Cortez, Valerie, Dallas, Ronald H., Fabrizio, Thomas, Freiden, Pamela, Gowen, Ashleigh, Hodges, Jason, Kirk, Allison M., Roubidoux, Ericka Kirkpatrick, Mettelman, Robert C., Russell-Bell, Jamie, Souquette, Aisha, Sparks, James, Van de Velde, Lee-Ann, Vazquez-Pagan, Ana, Whitt, Kendall, Wilson, Taylor L., Wittman, David E., Wohlgemuth, Nicholas, Wu, Gang, Taylor, Charles, Molina-Paris, Carmen, Schultz-Cherry, Stacey, Tang, Li, Thomas, Paul G., McGargill, Maureen A.
• Format: Article
• Language: English
• Subjects: 229E; Animals; Antibodies, Viral - immunology; antibody; Antibody Formation - immunology; Asymptomatic Infections; Case-Control Studies; Cell Line; Common Cold - immunology; Common Cold - virology; COVID-19; COVID-19 - immunology; COVID-19 - virology; Cross Reactions - immunology; Female; HEK293 Cells; HKU1; Humans; Immunity, Humoral - immunology; Mice; Mice, Inbred C57BL; NL63; OC43; pre-existing immunity; SARS-CoV-2; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - immunology
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2021.12.005

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. [Display omitted] •We assess human common cold CoV (hCCCoV) antibodies before and after SARS-CoV-2 infection•Betacoronavirus hCCCoV antibodies are boosted after SARS-CoV-2 infection•Baseline hCCCoV antibodies do not protect against SARS-CoV-2 infection•Pre-existing hCCCoV antibodies may hinder effective immunity against SARS-CoV-2 A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoVs) impacts susceptibility to SARS-CoV-2 infection. Lin et al. analyze hCCCoV antibodies in the same individuals before and after SARS-CoV-2 infection, finding pre-existing betacoronavirus antibodies may hinder SARS-CoV-2-effective immunity following infection.