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

Autor: Dos Santos Alves RP; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Timis J; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Miller R; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Valentine K; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Pinto PBA; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Gonzalez A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Regla-Nava JA; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.; Department of Microbiology and Pathology, University Center for Health Science (CUCS), University of Guadalajara, Guadalajara, 44340, Mexico., Maule E; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Nguyen MN; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Shafee N; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Landeras-Bueno S; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Olmedillas E; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Laffey B; Microscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USA., Dobaczewska K; Microscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USA., Mikulski Z; Microscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USA., McArdle S; Microscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USA., Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Kim K; Histopathology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USA., Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Ollmann Saphire E; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA., Elong Ngono A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA. aelong@lji.org., Shresta S; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA. sujan@lji.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jan 26; Vol. 15 (1), pp. 787. Date of Electronic Publication: 2024 Jan 26.
DOI: 10.1038/s41467-024-45043-2
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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