Pre-existing YFV-17D immunity mediates T cell cross-protection against dengue virus serotype 2 infection in mice
Widespread yellow fever virus (YFV) immunity in Sub-Saharan Africa may mitigate orthoflavivirus outbreaks. Here, we investigate whether pre-existing YFV-17D immunity confers cross-protection against dengue virus serotype 2 (DENV-2) infection in a murine model. IFNAR1<sup>-/-</sup> mice immunized with YFV-17D exhibited significantly reduced DENV-2 viremia, weight loss, and disease severity, with improved survival compared to naïve controls. Mechanistic studies revealed that cross-protection was mediated by heterologous T cell responses rather than cross-binding antibodies. Depletion of T cells in YFV-17D-immune mice prior to DENV-2 challenge resulted in increased viremia, weight loss, and disease severity, underscoring the protective role of YFV-17D-elicited T cell immunity. Furthermore, YFV-17D-specific T cells displayed cytotoxicity against DENV NS3- and NS5-pulsed cells, demonstrating their functional role in viral control. These findings highlight the critical contribution of heterologous T cell immunity in YFV-17D-mediated protection against DENV-2 and suggest that vaccines designed to elicit T cell responses could enhance cross-protection against orthoflavivirus infections.
Authors
- Yifeng Ding (ORCID: https://orcid.org/0000-0001-9926-1398)
- Prince Baffour Tonto (ORCID: https://orcid.org/0000-0001-8328-9062)
- Wei‐Kung Wang (ORCID: https://orcid.org/0000-0002-6670-4663)
- Reem Alatrash (ORCID: https://orcid.org/0009-0002-0328-1277)
- Bobby Brooke Herrera
- Sebastian Gallon
Institutions
- Rutgers, The State University of New Jersey (US)
- University of Hawaiʻi at Mānoa (US)
- Johnson University (US)
- Rutgers Sexual and Reproductive Health and Rights (NL)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-09-02
- DOI
- https://doi.org/10.1038/s42003-025-08793-3
- Citations
- 1
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 1.88
Funders
- New Jersey Health Foundation
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey
- National Institute of Allergy and Infectious Diseases