Tanelus, ManetteLópez, KrisangelSmith, ShaanMuller, John A.Porier, Danielle L.Auguste, Dawn I.Stone, William B.Paulson, Sally L.Auguste, Albert J.2024-01-162024-01-162023-12-012045-2322https://hdl.handle.net/10919/117365Zika virus (ZIKV) is an important re-emerging flavivirus that presents a significant threat to human health worldwide. Despite its importance, no vaccines are approved for use in humans. Insect-specific flaviviruses (ISFVs) have recently garnered attention as an antigen presentation platform for vaccine development and diagnostic applications. Here, we further explore the safety, immunogenicity, and efficacy of a chimeric ISFV-Zika vaccine candidate, designated Aripo-Zika (ARPV/ZIKV). Our results show a near-linear relationship between increased dose and immunogenicity, with 1011 genome copies (i.e., 108 focus forming units) being the minimum dose required for protection from ZIKV-induced morbidity and mortality in mice. Including boosters did not significantly increase the short-term efficacy of ARPV/ZIKV-vaccinated mice. We also show that weanling mice derived from ARPV/ZIKV-vaccinated dams were completely protected from ZIKV-induced morbidity and mortality upon challenge, suggesting efficient transfer of maternally-derived protective antibodies. Finally, in vitro coinfection studies of ZIKV with Aripo virus (ARPV) and ARPV/ZIKV in African green monkey kidney cells (i.e., Vero-76) showed that ARPV and ARPV/ZIKV remain incapable of replication in vertebrate cells, despite the presence of active ZIKV replication. Altogether, our data continue to support ISFV-based vaccines, and specifically the ARPV backbone is a safe, immunogenic and effective vaccine strategy for flaviviruses.application/pdfenCreative Commons Attribution 4.0 InternationalInfectious DiseasesAnimalsHumansMiceViral VaccinesAntibodies, ViralAntibodies, NeutralizingZika VirusZika Virus InfectionImmunogenicity, VaccineChlorocebus aethiopsArticle - Refereedhttps://doi.org/10.1038/s41598-023-47086-9131Auguste, Albert [0000-0001-9048-0041]Muller, John [0000-0001-5754-5560]Paulson, Sally [0000-0003-4206-9279]379684432045-2322