Dong-Bo Jiang1, Li-Juan Sun2, Lin-Feng Cheng3, Jin-Peng Zhang1, Shao-Bo Xiao1, Yuan-Jie Sun1, Shu-Ya Yang1, Jing Wang1, Fang-Lin Zhang4, Kun Yang5. 1. Department of Immunology, Fourth Military Medical University, No.169, Changle W. Rd., Xi'an, 710032, China. 2. Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, No.169, Changle W. Rd., Xi'an, 710032, China. 3. Department of Microbiology, Fourth Military Medical University, No.169, Changle W. Rd., Xi'an, 710032, China. 4. Department of Microbiology, Fourth Military Medical University, No.169, Changle W. Rd., Xi'an, 710032, China. Electronic address: flzhang@fmmu.edu.cn. 5. Department of Immunology, Fourth Military Medical University, No.169, Changle W. Rd., Xi'an, 710032, China. Electronic address: yangkunkun@fmmu.edu.cn.
Abstract
BACKGROUND: Prophylaxis 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 & RESULTS: Immune 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. CONCLUSION: pVAX-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.
BACKGROUND: Prophylaxis 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 & RESULTS: Immune 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. CONCLUSION: pVAX-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.