Prefusion-stabilized Hantaan virus glycoprotein nucleic acid vaccine elicits potent neutralizing antibody responses via germinal center activation
- Wei Ye
- Yamei Dang
- Yuan Wang
- Qiqi Yang
- Hui Zhang
- Chuantao Ye
- Jing Wei
- Jiawei Pei
- Xuemin Pei
- Dongshen Jiang
- Xiaojing Yang
- Xiaolei Jin
- Hongwei Ma
- He Liu
- Liang Zhang
- Linfeng Cheng
- Yangchao Dong
- Yingfeng Lei
- Zhikai Xu
- Fanglin Zhang
2026-03-14
Old World orthohantaviruses , including Hantaan virus (HTNV), cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Available inactivated vaccines often induce low neutralizing antibodies and short-term protection. We evaluated nucleic acid vaccines expressing a prefusion-stabilized HTNV glycoprotein in female BALB/c mice. Both DNA and mRNA-LNP versions elicited robust neutralizing antibodies by strongly activating germinal centers, which protected mice against high-dose HTNV challenge. We further tested heterologous prime-boost regimens, where mice primed with inactivated vaccine received different boosters. All boosters increased neutralizing titers, but only the prefusion-stabilized glycoprotein mRNA-LNP vaccine raised titers to the level achieved by its own full primary vaccination course. This demonstrates the immunogen’s superiority in developing next-generation vaccines and its unique ability to potently recall memory B cells induced by suboptimal inactivated vaccines. Thus, prefusion-stabilized glycoprotein-based nucleic acid vaccines are promising candidates for advanced orthohantavirus vaccine development.