TY - JOUR TI - CD8+ T cells mediate protection against Zika virus induced by an NS3-based vaccine AU - Ngono, Annie Elong AU - Syed, Thasneem AU - Nguyen, Anh-Viet AU - Regla-Nava, Jose Angel AU - Susantono, Mercylia AU - Spasova, Darina AU - Aguilar, Allison AU - West, Melissa AU - Sparks, Jessica AU - Gonzalez, Andrew AU - Branche, Emilie AU - DeHart, Jason L. AU - Vega, Jerel Boyd AU - Karmali, Priya Prakash AU - Chivukula, Padmanabh AU - Kamrud, Kurt AU - Aliahmad, Parinaz AU - Wang, Nathaniel AU - Shresta, Sujan T2 - Science Advances AB - Zika virus (ZIKV) is associated with congenital malformations in infants born to infected mothers, and with Guillain-Barré syndrome in infected adults. Development of ZIKV vaccines has focused predominantly on the induction of neutralizing antibodies, although a suboptimal antibody response may theoretically enhance disease severity through antibody-dependent enhancement (ADE). Here, we report induction of a protective anti-ZIKV CD8+ T cell response in the HLA-B*0702 Ifnar1−/− transgenic mice using an alphavirus-based replicon RNA vaccine expressing ZIKV nonstructural protein NS3, a potent T cell antigen. The NS3 vaccine did not induce a neutralizing antibody response but elicited polyfunctional CD8+ T cells that were necessary and sufficient for preventing death in lethally infected adult mice and fetal growth restriction in infected pregnant mice. These data identify CD8+ T cells as the major mediators of ZIKV NS3 vaccine–induced protection and suggest a new strategy to develop safe and effective anti-flavivirus vaccines. The crucial role of CD8+ T cells in vaccine-mediated protection is a valuable evidence for new insights in vaccine development. The crucial role of CD8+ T cells in vaccine-mediated protection is a valuable evidence for new insights in vaccine development. DA - 2020/11/01/ PY - 2020 DO - 10.1126/sciadv.abb2154 DP - advances.sciencemag.org VL - 6 IS - 45 SP - eabb2154 LA - en SN - 2375-2548 UR - https://advances.sciencemag.org/content/6/45/eabb2154 Y2 - 2020/11/06/22:39:32 ER -