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<p>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&#xa0;in a murine model. <i>IFNAR1</i><sup><i>-/-</i></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.</p>

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Pre-existing YFV-17D immunity mediates T cell cross-protection against dengue virus serotype 2 infection in mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月2日

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  • Prince Baffour Tonto,
  • Sebastian Gallon,
  • Reem Alatrash,
  • Yifeng Ding,
  • Wei-Kung Wang,
  • Bobby Brooke Herrera

摘要

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-/- 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.