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ACS Nano . An Intranasal Multivalent Epitope-Based Nanoparticle Vaccine Confers Broad Protection against Divergent Influenza Viruses

tetano

Editor, Senior Moderator
ACS Nano


. 2023 Jul 3.
doi: 10.1021/acsnano.3c01829. Online ahead of print. An Intranasal Multivalent Epitope-Based Nanoparticle Vaccine Confers Broad Protection against Divergent Influenza Viruses

Jingdi Pan[SUP] 1 2 [/SUP], Qihui Wang[SUP] 1 2 [/SUP], Mi Qi[SUP] 1 2 [/SUP], Jianjun Chen[SUP] 1 2 [/SUP], Xuefan Wu[SUP] 1 2 [/SUP], Xiaowei Zhang[SUP] 1 2 [/SUP], Wei Li[SUP] 1 2 [/SUP], Xian-En Zhang[SUP] 3 [/SUP], Zongqiang Cui[SUP] 1 2 [/SUP]



Affiliations
Abstract

The development of a universal influenza vaccine to control public health threats from circulating and emerging influenza viruses is highly desirable. Here we report an intranasal multivalent epitope-based nanoparticle vaccine with broad protection against divergent influenza A and B viruses. Three highly conserved epitopes consisting of the A α-helix of hemagglutinin (H), the ectodomain of matrix protein 2 (M) and the HCA-2 of neuraminidase (N) are presented on a self-assembling recombinant human heavy chain ferritin cage (F) to generate the HMNF nanoparticle. Intranasal immunization of mice with HMNF mobilized potent immune responses, including high levels of antigen-specific antibodies and T cell-mediated responses, which exhibited cross-reactivity to various antigen mutations. Vaccination with HMNF conferred full protection against lethal challenge with divergent influenza A and B viruses. The broad protection of HMNF nanoparticles could be attributed to the synergistic function of antibodies and T cells. Moreover, the induced immune responses are long-lasting, and protection is maintained six months after vaccination. Our constructed HMNF nanoparticle can serve as a promising candidate for a universal influenza vaccine.

Keywords: Ferritin; Influenza virus; Multivalent epitopes; Nanoparticle vaccine; Universal influenza vaccine.

 
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