Lentiviral vector-based T-cell vaccines against Zika and yellow fever viruses

Zika and yellow fever flaviviruses induce important human diseases, mainly in tropical regions. Zika virus is an emerging pathogen that has recently spread to new geographic areas, while yellow fever virus, effectively controlled in the past, has recently re-emerged and caused outbreaks in endemic regions. Since antibody-based vaccines could potentially increase the severity of infections by the related Zika and dengue viruses via antibody-dependent enhancement, new vaccine approaches need to be explored. Here, we described lentiviral vectors that express antigens based on T-cell epitope-containing regions of Zika and yellow fever viruses and evaluated the immunogenicity and protective efficacy induced by these vectors in an ifnar-/- mouse model. These vectors induced T-cell responses in the absence of infection-enhancing antibodies and demonstrated significant protection against the two pathogens, associated with reduced viremia and viral load in organs, as well as protection against weight loss and organ pathology.