Recombinant DNA vaccine of Hantavirus Gn and LAMP1 induced long-term immune protection in mice

•Hantavirus (HTV) DNA vaccine pVAX-LAMP/Gn established memory immune responses.•Only pVAX-LAMP/Gn gained long-term seroconversion compared with inactivated vaccine.•Enhanced CTL cytotoxicity and Th IFN-γ activity defined cellular memory immunity.•Epitope-spreading phenomenon suggested cross-species T-cell hot-spot on Hantaan virus Gn.•Safety of pVAX-LAMP/Gn was reconfirmed through behavioral and histological analysis.

BackgroundProphylaxis is widely adopted the best choice against Hemorrhagic fever with renal syndrome (HFRS) caused by Hantavirus. However, loss of memory immune response maintenance remains as major shortcoming in current HFRS vaccine. A recombinant DNA vaccine, pVAX-LAMP/Gn was previously proved efficient, requiring long-term evaluations.Methods & resultsImmune responses of Balb/c mice were assessed by specific and neutralizing antibodies, interferon-γ ELISpot assay, and cytotoxic T-lymphocyte cytotoxicity assay. HTNV-challenge assay identified long-term protection. Safety was confirmed by histological and behavioral analysis. Epitope-spreading phenomenon was noted, revealing two sets of dominant T-cell epitopes cross-species.ConclusionpVAX-LAMP/Gn established memory responses within a long-term protection. Lysosome-targeted strategy showed promise on Gn-based DNA vaccine and further investigations are warranted in other immunogenic Hantaviral antigens.