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<p>Old World <i>orthohantaviruses</i>, 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 <i>orthohantavirus</i> vaccine development.</p>

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Prefusion-stabilized Hantaan virus glycoprotein nucleic acid vaccine elicits potent neutralizing antibody responses via germinal center activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月14日

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  • 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

摘要

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.