Self-assembled multiepitope nanovaccine based on NoV P particles induces effective and lasting protection against H3N2 influenza virus

Abstract

Current seasonal influenza vaccines confer only limited coverage of virus strains due to the frequent genetic and antigenic variability of influenza virus (IV). Epitope vaccines that accurately target conserved domains provide a promising approach to increase the breadth of protection; however, poor immunogenicity greatly hinders their application. The protruding (P) domain of the norovirus (NoV), which can self-assemble into a 24-mer particle called the NoV P particle, offers an ideal antigen presentation platform. In this study, a multiepitope nanovaccine displaying influenza epitopes (HMN-PP) was constructed based on the NoV P particle nanoplatform. Large amounts of HMN-PP were easily expressed in Escherichia coli in soluble form. Animal experiments showed that the adjuvanted HMN-PP nanovaccine induced epitope-specific antibodies and haemagglutinin (HA)-specific neutralizing antibodies, and the antibodies could persist for at least three months after the last immunization. Furthermore, HMN-PP induced matrix protein 2 extracellular domain (M2e)-specific antibody-dependent cell-mediated cytotoxicity, CD4 + and CD8 + T-cell responses, and a nucleoprotein (NP)-specific cytotoxic T lymphocyte (CTL) response. These results indicated that the combination of a multiepitope vaccine and self-assembled NoV P particles may be an ideal and effective vaccine strategy for highly variable viruses such as IV and SARS-CoV-2. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s12274-023-5395-6.

Self‐Assembled Multiepitope Nanovaccine Provides Long‐Lasting Cross‐Protection against Influenza Virus

“…Our previous studies have demonstrated that the ADCC activity induced by M2e also contributed to the protection against IAV. [ 38 ] In this study, to further improve the targeting and efficacy of epitope vaccines, we designed and constructed multiepitope nanovaccines based on HA2 and M2e, using ferritin as the delivery vehicle. We retrieved 364 sequences of H3N2 M2 and 320 sequences of H1N1 M2, from1968 to 2020, and the M2e sequences were reserved and aligned.…”

Multi-epitope vaccine design for hepatitis E virus based on protein ORF2 and ORF3

“…The EBV polyepitope vaccine, which includes 20 CD8 + T-cell epitopes, induces high frequencies of CD4 + T cells and CD8 + T cells, which are maintained for more than 7 months ( Dasari et al, 2023 ). It has been reported that the norovirus (NoV) P particle, a 24-self-assembly of the protruding domain, displays H16, M2e, and NP9 on its surface, which elicit long-lasting hemagglutinin (HA)-specific neutralizing antibodies, M2e-CD4 + and CD8 + T-cell responses, and a nucleoprotein-specific CTL response, respectively ( Nie et al, 2023 ).…”