Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice

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  • Dos Santos Alves, Rúbens Prince
    • Other Affiliation: La Jolla Institute for Immunology
  • Timis, Julia
    • Other Affiliation: La Jolla Institute for Immunology
  • Miller, Robyn
    • Other Affiliation: La Jolla Institute for Immunology
  • Valentine, Kristen
    • Other Affiliation: La Jolla Institute for Immunology
  • Pinto, Paolla Beatriz Almeida
    • Other Affiliation: La Jolla Institute for Immunology
  • Gonzalez, Andrew
    • Other Affiliation: La Jolla Institute for Immunology
  • Regla-Nava, Jose Angel
    • Other Affiliation: La Jolla Institute for Immunology
  • Maule, Erin
    • Other Affiliation: La Jolla Institute for Immunology
  • Nguyen, Michael N.
    • Other Affiliation: La Jolla Institute for Immunology
  • Shafee, Norazizah
    • Other Affiliation: La Jolla Institute for Immunology
  • Landeras-Bueno, Sara
    • Other Affiliation: La Jolla Institute for Immunology
  • Olmedillas, Eduardo
    • Other Affiliation: La Jolla Institute for Immunology
  • Laffey, Brett
    • Other Affiliation: La Jolla Institute for Immunology
  • Dobaczewska, Katarzyna
    • Other Affiliation: La Jolla Institute for Immunology
  • Mikulski, Zbigniew
    • Other Affiliation: La Jolla Institute for Immunology
  • McArdle, Sara
    • Other Affiliation: La Jolla Institute for Immunology
  • Leist, Sarah R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Kim, Kenneth
    • Other Affiliation: La Jolla Institute for Immunology
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Ollmann Saphire, Erica
    • Other Affiliation: La Jolla Institute for Immunology
  • Elong Ngono, Annie
    • Other Affiliation: La Jolla Institute for Immunology
  • Shresta, Sujan
    • Other Affiliation: La Jolla Institute for Immunology
Abstract
  • SARS-CoV-2-reactive T cells are detected in some healthy unexposed individuals. Human studies indicate these T cells could be elicited by the common cold coronavirus OC43. To directly test this assumption and define the role of OC43-elicited T cells that are cross-reactive with SARS-CoV-2, we develop a model of sequential infections with OC43 followed by SARS-CoV-2 in HLA-B*0702 and HLA-DRB1*0101 Ifnar1-/- transgenic mice. We find that OC43 infection can elicit polyfunctional CD8+ and CD4+ effector T cells that cross-react with SARS-CoV-2 peptides. Furthermore, pre-exposure to OC43 reduces subsequent SARS-CoV-2 infection and disease in the lung for a short-term in HLA-DRB1*0101 Ifnar1-/- transgenic mice, and a longer-term in HLA-B*0702 Ifnar1-/- transgenic mice. Depletion of CD4+ T cells in HLA-DRB1*0101 Ifnar1-/- transgenic mice with prior OC43 exposure results in increased viral burden in the lung but no change in virus-induced lung damage following infection with SARS-CoV-2 (versus CD4+ T cell-sufficient mice), demonstrating that the OC43-elicited SARS-CoV-2 cross-reactive T cell-mediated cross-protection against SARS-CoV-2 is partially dependent on CD4+ T cells. These findings contribute to our understanding of the origin of pre-existing SARS-CoV-2-reactive T cells and their effects on SARS-CoV-2 clinical outcomes, and also carry implications for development of broadly protective betacoronavirus vaccines.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Nature Communications
Journal volume
  • 15
Journal issue
  • 1
Page start
  • 787
Language
  • English
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  • Publisher
ISSN
  • 2041-1723
Publisher
  • Springer Nature

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