Persistent Zika Virus Clinical Susceptibility despite Reduced Viral Burden in Mice with Expanded Virus-Specific CD8+ T Cells Primed by Recombinant Listeria monocytogenes

Vaccines against Zika virus (ZIKV) infection that target CD8 + T cells are of considerable interest because Abs may enhance infection susceptibility. However, whether CD8 + T cells are protective or promote susceptibility to clinical infection symptoms remains uncertain. To more precisely investigate ZIKV-specific CD8 + T cells in isolation, we engineered a Listeria monocytogenes -based vector to express a single MHC class I-restricted immune dominant peptide, E294-302, from ZIKV envelope protein. We show accumulation of activated ZIKV-specific CD8 + T cells primed by recombinant L. monocytogenes is associated with reductions in circulating virus levels after ZIKV challenge in type I IFN receptor-deficient mice and wildtype mice administered neutralizing Abs against type I IFN receptor. Interestingly, susceptibility to ZIKV clinical infection including weight loss and mortality each persists and is neither significantly improved nor worsened compared with isogenic L. monocytogenes -primed control mice. These data demonstrating persistent ZIKV clinical susceptibility despite reduced viral burden in mice with expanded virus-specific CD8 + T cells highlights the need for targeting other adaptive immune components in developing vaccines against ZIKV infection.