tetano
Editor, Senior Moderator
Nat Commun
. 2024 Jan 26;15(1):787.
doi: 10.1038/s41467-024-45043-2. Human coronavirus OC43-elicited CD4[SUP]+[/SUP] T cells protect against SARS-CoV-2 in HLA transgenic mice
Rúbens Prince Dos Santos Alves[SUP] 1 [/SUP], Julia Timis[SUP] 1 [/SUP], Robyn Miller[SUP] 1 [/SUP], Kristen Valentine[SUP] 1 [/SUP], Paolla Beatriz Almeida Pinto[SUP] 1 [/SUP], Andrew Gonzalez[SUP] 1 [/SUP], Jose Angel Regla-Nava[SUP] 1 2 [/SUP], Erin Maule[SUP] 1 [/SUP], Michael N Nguyen[SUP] 1 [/SUP], Norazizah Shafee[SUP] 1 [/SUP], Sara Landeras-Bueno[SUP] 1 [/SUP], Eduardo Olmedillas[SUP] 1 [/SUP], Brett Laffey[SUP] 3 [/SUP], Katarzyna Dobaczewska[SUP] 3 [/SUP], Zbigniew Mikulski[SUP] 3 [/SUP], Sara McArdle[SUP] 3 [/SUP], Sarah R Leist[SUP] 4 [/SUP], Kenneth Kim[SUP] 5 [/SUP], Ralph S Baric[SUP] 4 6 [/SUP], Erica Ollmann Saphire[SUP] 1 7 [/SUP], Annie Elong Ngono[SUP] 8 [/SUP], Sujan Shresta[SUP] 9 [/SUP]
Affiliations
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[SUP]-/-[/SUP] transgenic mice. We find that OC43 infection can elicit polyfunctional CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] 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[SUP]-/-[/SUP] transgenic mice, and a longer-term in HLA-B*0702 Ifnar1[SUP]-/-[/SUP] transgenic mice. Depletion of CD4[SUP]+[/SUP] T cells in HLA-DRB1*0101 Ifnar1[SUP]-/-[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] 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 Jan 26;15(1):787.
doi: 10.1038/s41467-024-45043-2. Human coronavirus OC43-elicited CD4[SUP]+[/SUP] T cells protect against SARS-CoV-2 in HLA transgenic mice
Rúbens Prince Dos Santos Alves[SUP] 1 [/SUP], Julia Timis[SUP] 1 [/SUP], Robyn Miller[SUP] 1 [/SUP], Kristen Valentine[SUP] 1 [/SUP], Paolla Beatriz Almeida Pinto[SUP] 1 [/SUP], Andrew Gonzalez[SUP] 1 [/SUP], Jose Angel Regla-Nava[SUP] 1 2 [/SUP], Erin Maule[SUP] 1 [/SUP], Michael N Nguyen[SUP] 1 [/SUP], Norazizah Shafee[SUP] 1 [/SUP], Sara Landeras-Bueno[SUP] 1 [/SUP], Eduardo Olmedillas[SUP] 1 [/SUP], Brett Laffey[SUP] 3 [/SUP], Katarzyna Dobaczewska[SUP] 3 [/SUP], Zbigniew Mikulski[SUP] 3 [/SUP], Sara McArdle[SUP] 3 [/SUP], Sarah R Leist[SUP] 4 [/SUP], Kenneth Kim[SUP] 5 [/SUP], Ralph S Baric[SUP] 4 6 [/SUP], Erica Ollmann Saphire[SUP] 1 7 [/SUP], Annie Elong Ngono[SUP] 8 [/SUP], Sujan Shresta[SUP] 9 [/SUP]
Affiliations
- PMID: 38278784
- PMCID: PMC10817949
- DOI: 10.1038/s41467-024-45043-2
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[SUP]-/-[/SUP] transgenic mice. We find that OC43 infection can elicit polyfunctional CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] 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[SUP]-/-[/SUP] transgenic mice, and a longer-term in HLA-B*0702 Ifnar1[SUP]-/-[/SUP] transgenic mice. Depletion of CD4[SUP]+[/SUP] T cells in HLA-DRB1*0101 Ifnar1[SUP]-/-[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] 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.