Porier, Danielle L.Wilson, Sarah N.Auguste, Dawn I.Leber, AndrewCoutermarsh-Ott, SherylAllen, Irving C.Caswell, Clayton C.Budnick, James A.Bassaganya-Riera, JosepHontecillas, RaquelWeger-Lucarelli, JamesWeaver, Scott C.Auguste, A. Jonathan2021-10-132021-10-132021-10-07Porier, D.L.; Wilson, S.N.; Auguste, D.I.; Leber, A.; Coutermarsh-Ott, S.; Allen, I.C.; Caswell, C.C.; Budnick, J.A.; Bassaganya-Riera, J.; Hontecillas, R.; Weger-Lucarelli, J.; Weaver, S.C.; Auguste, A.J. Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine. Vaccines 2021, 9, 1142.http://hdl.handle.net/10919/105279Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation <i>in vitro</i> and showed no hematological, histological or pathogenic effects <i>in vivo</i>. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and -compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4⁺ and CD8⁺ responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.application/pdfenCreative Commons Attribution 4.0 Internationalflavivirusinsect-specific virusvaccineZika viruscorrelates of protectionArticle - Refereed2021-10-12https://doi.org/10.3390/vaccines9101142