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NS1 DNA vaccination protects against Zika infection through T cell-mediated immunity in immunocompetent mice.

  • Author(s): Grubor-Bauk, B;
  • Wijesundara, DK;
  • Masavuli, M;
  • Abbink, P;
  • Peterson, RL;
  • Prow, NA;
  • Larocca, RA;
  • Mekonnen, ZA;
  • Shrestha, A;
  • Eyre, NS;
  • Beard, MR;
  • Gummow, J;
  • Carr, J;
  • Robertson, SA;
  • Hayball, JD;
  • Barouch, DH;
  • Gowans, EJ
  • et al.
Abstract

The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell-based ZIKV vaccines.

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