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

tetano

Editor, Senior Moderator
J Nanobiotechnology


. 2025 Jul 3;23(1):483.
doi: 10.1186/s12951-025-03582-w. Targeting heptad repeats and fusion peptide: nanoparticle vaccine elicits mucosal immune response against SARS-CoV-2 variants

Chaofeng Liang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Rong Li[SUP] #[/SUP][SUP] 3 4 [/SUP], Zeyu Pu[SUP] #[/SUP][SUP] 3 [/SUP], Ran Chen[SUP] #[/SUP][SUP] 3 [/SUP], Yuzhuang Li[SUP] #[/SUP][SUP] 3 [/SUP], Siqi Chen[SUP] #[/SUP][SUP] 3 [/SUP], Jinzhu Feng[SUP] 3 [/SUP], Jie Liu[SUP] 3 [/SUP], Yuteng Bai[SUP] 3 [/SUP], Xuewen Qin[SUP] 3 [/SUP], Chengjie Xie[SUP] 3 [/SUP], Yixin Zhang[SUP] 3 [/SUP], Yi Peng[SUP] 3 [/SUP], Hui Tang[SUP] 3 [/SUP], Mei Zhang[SUP] 3 [/SUP], Qiuyue Zhang[SUP] 5 [/SUP], Tao Wang[SUP] 3 [/SUP], Baisheng Li[SUP] 4 [/SUP], Huan Zhang[SUP] 4 [/SUP], Xu Zhang[SUP] 3 [/SUP], Yun He[SUP] 5 [/SUP], Xin He[SUP] 3 [/SUP], Ting Pan[SUP] 3 [/SUP], Hui Zhang[SUP] 3 [/SUP], Yiwen Zhang[SUP] 6 [/SUP]



Affiliations
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 (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.

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

 
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