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

• Published in: Journal of nanobiotechnology Vol. 23; no. 1; pp. 483 - 15
• Main Authors: Liang, Chaofeng, Li, Rong, Pu, Zeyu, Chen, Ran, Li, Yuzhuang, Chen, Siqi, Feng, Jinzhu, Liu, Jie, Bai, Yuteng, Qin, Xuewen, Xie, Chengjie, Zhang, Yixin, Peng, Yi, Tang, Hui, Zhang, Mei, Zhang, Qiuyue, Wang, Tao, Li, Baisheng, Zhang, Huan, Zhang, Xu, He, Yun, He, Xin, Pan, Ting, Zhang, Hui, Zhang, Yiwen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.07.2025; BioMed Central; BMC
• Subjects: Administration, Intranasal; Animals; Antibodies, Viral - immunology; Antigenic determinants; Broad-spectrum vaccine; Bronchoalveolar Lavage Fluid - immunology; Conserved epitopes; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 - virology; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; Female; Health aspects; Humans; Immune response; Immunity, Mucosal - immunology; Immunoglobulin G - immunology; Lung - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mucosal immunity; Nanoparticle vaccine; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanovaccines; Peptides; Pharmaceutical research; Respiratory viruses; SARS-CoV-2; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; China; Respiratory viruses; Broad-spectrum vaccine; Conserved epitopes; SARS-CoV-2; Mucosal immunity; Nanoparticle vaccine
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-025-03582-w

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 ) and resident memory T cells (T ) 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.