Recombinant Japanese Encephalitis Virus Envelope Antigen Presented on CoPoP Liposomes Elicits Cellular Immunity and Protects Mice From Lethal Challenge.

Go to: Abstract Japanese encephalitis virus (JEV) causes severe encephalitis in endemic regions, and vaccination remains the primary preventive measure. To develop subunit vaccines that enhance cellular immunity, we produced a soluble His–tagged recombinant JEV envelope (rJEV-E) ectodomain and particularized it on cobalt porphyrin–phospholipid (CoPoP) immunogenic liposomes containing an monophosphoryl lipid A-related TLR4 agonist, with or without Quillaja saponaria saponin fraction 21 (QS-21). CoPoP-mediated particleization enabled stable antigen display and, when combined with QS-21 (rJEV-E/ECLSQ), elicited Th1-biased CD4 + and CD8 + T-cell IFN-γ responses alongside functional neutralizing Abs. In a stringent intracerebral lethal challenge model, rJEV-E/ECLSQ conferred robust protection despite moderate 50% plaque reduction neutralization test titers. JEV-specific IgG responses were sustained for at least one year, with recallable cellular immunity upon late boosting. These findings demonstrate that CoPoP-based particleization enables qualitative modulation of vaccine-induced immunity while maintaining effective protection in a stringent challenge setting.