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

Med

42 Pages Posted: 20 May 2021 Publication Status: Review Complete

See all articles by Vijayashree Mysore

Vijayashree Mysore

Harvard University - Department of Pathology

Xavier Cullere

Harvard University - Department of Pathology

Matthew Settles

University of California, Davis - Genome Center

Xinge Ji

Cleveland Clinic

Michael W. Kattan

Cleveland Clinic - Department of Quantitative Health Sciences

Michaël Desjardins

Harvard University - Department of Medicine

Blythe Durbin-Johnson

University of California, Davis - Genome Center

Tal Gilboa

Harvard University - Department of Pathology

Lindsey Baden

Harvard University - Department of Medicine

David Walt

Harvard University - Department of Pathology

Andrew Lichtman

Harvard University - Department of Pathology

Lara Jehi

Cleveland Clinic - Neurological Institute

Tanya Mayadas

Harvard University - Department of Pathology

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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 with 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.

Funding: 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.)

Declaration 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.

Ethical 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).

Keywords: SARS-CoV-2, heterologous immunity, antigens, vaccines, memory T cells, TCR repertoire, transcriptome, antigen presenting cells, risk prediction

Suggested Citation

Mysore, Vijayashree and Cullere, Xavier and Settles, Matthew and Ji, Xinge and Kattan, Michael W. and Desjardins, Michaël and Durbin-Johnson, Blythe and Gilboa, Tal and Baden, Lindsey and Walt, David and Lichtman, Andrew and Jehi, Lara and Mayadas, Tanya, Protective Heterologous T Cell Immunity in COVID-19 Induced by MMR and Tdap Vaccine Antigens. Available at SSRN: https://ssrn.com/abstract=3850361 or http://dx.doi.org/10.2139/ssrn.3850361
This version of the paper has not been formally peer reviewed.

Vijayashree Mysore

Harvard University - Department of Pathology ( email )

75 Francis St.
Boston, MA 02115
United States

Xavier Cullere

Harvard University - Department of Pathology ( email )

75 Francis St.
Boston, MA 02115
United States

Matthew Settles

University of California, Davis - Genome Center

451 Health Science Dr
Davis, CA 95616

Xinge Ji

Cleveland Clinic

9500 Euclid Ave.
Cleveland, OH 44195
United States

Michael W. Kattan

Cleveland Clinic - Department of Quantitative Health Sciences ( email )

Cleveland, OH
United States

Michaël Desjardins

Harvard University - Department of Medicine

Boston, MA 02115
United States

Blythe Durbin-Johnson

University of California, Davis - Genome Center

451 Health Science Dr
Davis, CA 95616

Tal Gilboa

Harvard University - Department of Pathology ( email )

75 Francis St.
Boston, MA 02115
United States

Lindsey Baden

Harvard University - Department of Medicine ( email )

Boston, MA 02115
United States

David Walt

Harvard University - Department of Pathology ( email )

75 Francis St.
Boston, MA 02115
United States

Andrew Lichtman

Harvard University - Department of Pathology ( email )

75 Francis St.
Boston, MA 02115
United States

Lara Jehi

Cleveland Clinic - Neurological Institute ( email )

6770 Mayfield Rd # 226
Cleveland, OH 44124
United States

Tanya Mayadas (Contact Author)

Harvard University - Department of Pathology ( email )

75 Francis St.
Boston, MA 02115
United States

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