Protective Heterologous T Cell Immunity in COVID-19 Induced by MMR and Tdap Vaccine Antigens

Abstract

T cells are critical for control of viral infection and effective vaccination. We investigated whether prior Measles-Mumps-Rubella (MMR) or Tetanus-Diphtheria-pertussis (Tdap) vaccination elicit cross-reactive T cells that mitigate COVID-19. Using co-cultures of antigen presenting cells (APC) loaded\xa0with antigens and autologous T cells, we found a high correlation between T cell responses to SARS-CoV-2 (Spike-S1 and Nucleocapsid) and MMR and Tdap vaccine proteins in both SARS-CoV-2 infected individuals and individuals immunized with mRNA-based SARS-CoV-2 vaccines. The overlapping T cell population contained effector memory T cells (T EMRA ) previously implicated in anti-viral immunity. TCR- and scRNA-sequencing detected cross-reactive clones with T EMRA features among the cells recognizing SARS-CoV-2, MMR and Tdap epitopes. A propensity-weighted analysis of 73,582 COVID-19 patients revealed that severe disease outcomes (hospitalization and transfer to intensive care unit or death) were reduced in MMR or Tdap vaccinated individuals by 38-32% and 23-20% respectively. In summary, Tdap and MMR memory T cell reactivated by SARS-CoV-2 provides protection against developing severe COVID-19 disease. \n \nFunding: This work was supported by National Institutes of Health R01HL065095 (T.M.), R01AI152522 (T.M.), R01NS097719 (L.J.) and a generous donation from Barbara and Amos Hostetter and the Chleck Foundation (D.R.W.) \n \nDeclaration of Interest: V.M., X.C., M.D., A.H.L., M.K., L.J. and T.M. declare that they have no competing interests to disclose. D.R.W has a financial interest in Quanterix Corporation, a company that develops an ultra-sensitive digital immunoassay platform. He is an inventor of the Simoa technology, founder of the company and serves on its Board of Directors. The anti-SARS-CoV-2 Simoa assays in this publication have been licensed by Brigham and Women’s Hospital to Quanterix Corporation. T.G. receives royalty payments from Brigham and Women’s Hospital for the antibodies assay technology. \n \nEthical Approval: All procedures performed were in accordance with ethical standards. Blood samples were obtained from consented healthy, self-reporting SARS-CoV-2 uninfected volunteers under a Mass General Brigham Institutional Review Board (IRB)-approved protocol (1999P001694). Patients signed informed consent to participate in a Mass General Brigham IRB-approved COVID-19 observational sample collection protocol (2020P000849).