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<p>The emergence of SARS-CoV-2 variants has underscored the urgent need for innovative vaccine strategies that provide robust and enduring protection against diverse strains. Our study introduces the FP-HR5 nanoparticle vaccine, designed to target the highly conserved S2 subunit of the spike protein, including the fusion peptide (FP) and heptad repeats (HR1 and HR2), using a 24-mer Helicobacter pylori ferritin platform. Administered intranasally, the FP-HR5-NP vaccine elicits robust systemic and mucosal immune responses in vivo, generating high titers of FP- and HR5-specific IgG antibodies. Notably, intranasal immunization resulted in elevated levels of secretory IgA and IgG in bronchoalveolar lavage fluid (BALF) and stimulated T-cell immune responses, significantly increasing resident memory B cells (B<sub>RM</sub>) and resident memory T cells (T<sub>RM</sub>) in the lungs. In hACE2 transgenic mice, three doses of FP-HR5-NP conferred substantial protection against Delta and Omicron variant challenges, with undetectable viral RNA levels in the lungs and no pathological changes observed. Overall, the FP-HR5-NP vaccine triggers comprehensive humoral and cellular immune responses at the mucosa, providing broad defense against SARS-CoV-2 variants and positioning it as a promising candidate for a universal COVID-19 vaccine solution.</p> Graphical abstract <p></p>

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Targeting heptad repeats and fusion peptide: nanoparticle vaccine elicits mucosal immune response against SARS-CoV-2 variants

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月3日

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  • Chaofeng Liang,
  • Rong Li,
  • Zeyu Pu,
  • Ran Chen,
  • Yuzhuang Li,
  • Siqi Chen,
  • Jinzhu Feng,
  • Jie Liu,
  • Yuteng Bai,
  • Xuewen Qin,
  • Chengjie Xie,
  • Yixin Zhang,
  • Yi Peng,
  • Hui Tang,
  • Mei Zhang,
  • Qiuyue Zhang,
  • Tao Wang,
  • Baisheng Li,
  • Huan Zhang,
  • Xu Zhang,
  • Yun He,
  • Xin He,
  • Ting Pan,
  • Hui Zhang,
  • Yiwen Zhang

摘要

The emergence of SARS-CoV-2 variants has underscored the urgent need for innovative vaccine strategies that provide robust and enduring protection against diverse strains. Our study introduces the FP-HR5 nanoparticle vaccine, designed to target the highly conserved S2 subunit of the spike protein, including the fusion peptide (FP) and heptad repeats (HR1 and HR2), using a 24-mer Helicobacter pylori ferritin platform. Administered intranasally, the FP-HR5-NP vaccine elicits robust systemic and mucosal immune responses in vivo, generating high titers of FP- and HR5-specific IgG antibodies. Notably, intranasal immunization resulted in elevated levels of secretory IgA and IgG in bronchoalveolar lavage fluid (BALF) and stimulated T-cell immune responses, significantly increasing resident memory B cells (BRM) and resident memory T cells (TRM) in the lungs. In hACE2 transgenic mice, three doses of FP-HR5-NP conferred substantial protection against Delta and Omicron variant challenges, with undetectable viral RNA levels in the lungs and no pathological changes observed. Overall, the FP-HR5-NP vaccine triggers comprehensive humoral and cellular immune responses at the mucosa, providing broad defense against SARS-CoV-2 variants and positioning it as a promising candidate for a universal COVID-19 vaccine solution.

Graphical abstract