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

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

  • J Nanobiotechnology. 2025 Jul 3;23(1):483. doi: 10.1186/s12951-025-03582-w.
Chaofeng Liang # 1 2 3,  Rong Li # 3 4,  Zeyu Pu # 3,  Ran Chen # 3,  Yuzhuang Li # 3,  Siqi Chen # 3,  Jinzhu Feng 3,  Jie Liu 3,  Yuteng Bai 3,  Xuewen Qin 3,  Chengjie Xie 3,  Yixin Zhang 3,  Yi Peng 3,  Hui Tang 3,  Mei Zhang 3,  Qiuyue Zhang 5,  Tao Wang 3,  Baisheng Li 4,  Huan Zhang 4,  Xu Zhang 3,  Yun He 5,  Xin He 3,  Ting Pan 3,  Hui Zhang 3,  Yiwen Zhang 6
Affiliations

Affiliations

  • 1 Graduate School of Guangzhou Medical University, Guangzhou, 510000, China.
  • 2 Guangzhou National Laboratory, Guangzhou, 510000, China.
  • 3 Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 4 Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, China.
  • 5 National Clinical Research Center for Infectious Diseases, The Second Affiliated Hospital of Southern, The Third People's Hospital of Shenzhen, University of Science and Technology, Shenzhen, 518112, Guangdong Province, China.
  • 6 Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. zhangyw57@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 40611257 DOI: 10.1186/s12951-025-03582-w
Abstract

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.

Keywords

Broad-spectrum vaccine; Conserved epitopes; Mucosal immunity; Nanoparticle vaccine; Respiratory viruses; SARS-CoV-2.

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