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<p>In the present study, by building on the previous development of a DC-SIGN-targeting virus-like structure (VLS) vaccine platform and a comprehensive characterization of SARS-CoV-2 structural biology, particularly insights into the role of the nucleocapsid (N) protein in eliciting cytotoxic T lymphocyte (CTL) responses during infection, we designed a SARS-CoV-2 virion-mimetic structural vaccine that encapsulates an mRNA encoding the spike S1 antigen complexed with N protein complexes, with S1 proteins loaded on its surface. This characterized virion-mimetic structural vaccine not only induces the production of high-efficiency antibodies against both the spike and N proteins but also elicits robust S1-specific and N-specific CTL responses in animal models. Furthermore, the generated antibodies exhibit cross-reactive neutralizing activity against multiple SARS-CoV-2 variants and provide protective immunity against challenge with mutant viruses in immunized hosts. This SARS-CoV-2 virion-mimetic structure effectively recapitulates natural infection pathways, comprehensively activating the innate immune system and thereby creating an optimal microenvironment for eliciting potent and broad-spectrum adaptive immune responses.</p>

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A synthetic virus-like assembly unlocks dual-antigen presentation for broad-spectrum anti-SARS-CoV-2 immunity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月22日

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  • Jingjing Zhang,
  • Fengyuan Zeng,
  • Yanmei Li,
  • Yixuan Wang,
  • Zhenxiao Zhang,
  • Changyong Mu,
  • Change Liu,
  • Yanrui Su,
  • Xiaowu Peng,
  • Lin Feng,
  • Dongxiu Gao,
  • Lichun Wang,
  • An Wang,
  • Miaomiao Xing,
  • Lihong Sun,
  • Zixiong Guo,
  • Huijuan Li,
  • Hui Zhang,
  • Xiaoxia Yu,
  • Bing Xie,
  • Lu Liu,
  • Liping He,
  • Zhixiao Zhang,
  • Dongbao Wang,
  • Fang Zhang,
  • Lichun Zheng,
  • Fuyun He,
  • Hongkun Yi,
  • Kaili Ma,
  • Qihan Li

摘要

In the present study, by building on the previous development of a DC-SIGN-targeting virus-like structure (VLS) vaccine platform and a comprehensive characterization of SARS-CoV-2 structural biology, particularly insights into the role of the nucleocapsid (N) protein in eliciting cytotoxic T lymphocyte (CTL) responses during infection, we designed a SARS-CoV-2 virion-mimetic structural vaccine that encapsulates an mRNA encoding the spike S1 antigen complexed with N protein complexes, with S1 proteins loaded on its surface. This characterized virion-mimetic structural vaccine not only induces the production of high-efficiency antibodies against both the spike and N proteins but also elicits robust S1-specific and N-specific CTL responses in animal models. Furthermore, the generated antibodies exhibit cross-reactive neutralizing activity against multiple SARS-CoV-2 variants and provide protective immunity against challenge with mutant viruses in immunized hosts. This SARS-CoV-2 virion-mimetic structure effectively recapitulates natural infection pathways, comprehensively activating the innate immune system and thereby creating an optimal microenvironment for eliciting potent and broad-spectrum adaptive immune responses.