T Cell Responses Correlate with Self-Reported Disease Severity and Neutralizing Antibody Responses Predict Protection against SARS-CoV-2 Breakthrough Infection
Zhen Zhao,
Attila Kumanovics,
Tanzy Love,
Stacy E. F. Melanson,
Qing H. Meng,
Alan H. B. Wu,
Joesph Wiencek,
Fred S. Apple,
Caitlin R. Ondracek,
David D. Koch,
Robert H. Christenson,
Yan Victoria Zhang
Affiliations
Zhen Zhao
Department of Laboratory Medicine and Pathology, Weill Cornell Medicine, New York, NY 10065, USA
Attila Kumanovics
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
Tanzy Love
Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642, USA
Stacy E. F. Melanson
Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Qing H. Meng
Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Alan H. B. Wu
Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
Joesph Wiencek
Department of Pathology, Microbiology and Immunology, Vanderbilt School of Medicine, Nashville, TN 37240, USA
Fred S. Apple
Department of Laboratory Medicine and Pathology, Hennepin Healthcare/Hennepin County Medical Center, Minneapolis, MN 55415, USA
Caitlin R. Ondracek
American Association for Clinical Chemistry, Washington, DC 22203, USA
David D. Koch
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30303, USA
Robert H. Christenson
Department of Pathology, University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD 21201, USA
Yan Victoria Zhang
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY 14642, USA
Objectives: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. Design and Methods: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. Results: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (<95 U/mL) predicted breakthrough infection, whereas previous infection, the type of vaccine, and T cell responses did not. T cell responses to viral epitopes (<0.120 IU/mL) showed a significant association with the self-reported severity of COVID-19 disease. Conclusion: This study provides evidence that NAb responses to SARS-CoV-2 vaccination correlate with protection against infection, whereas the T cell memory responses may contribute to protection against severe disease but not against infection.
