tetano
Editor, Senior Moderator
Adv Healthc Mater
. 2023 Nov 20:e2303531.
doi: 10.1002/adhm.202303531. Online ahead of print. Self-Assembled Multiepitope Nanovaccine Provides Long-Lasting Cross-Protection Against Influenza Virus
Jiaojiao Nie[SUP] 1 2 [/SUP], Qingyu Wang[SUP] 1 [/SUP], Chenxi Li[SUP] 1 [/SUP], Yongfei Zhou[SUP] 1 [/SUP], Xin Yao[SUP] 1 [/SUP], Lipeng Xu[SUP] 1 [/SUP], Yaotian Chang[SUP] 1 [/SUP], Fan Ding[SUP] 1 [/SUP], Lulu Sun[SUP] 1 [/SUP], Li Zhan[SUP] 1 [/SUP], Lvzhou Zhu[SUP] 1 [/SUP], Kunpeng Xie[SUP] 1 [/SUP], Xu Wang[SUP] 1 [/SUP], Yuhua Shi[SUP] 1 [/SUP], Qi Zhao[SUP] 2 3 [/SUP], Yaming Shan[SUP] 1 4 [/SUP]
Affiliations
Seasonal influenza vaccines typically provide strain-specific protection and are reformulated annually, which is a complex and time-consuming process. Multiepitope vaccines, combining multiple conserved antigenic epitopes from a pathogen, can trigger more robust, diverse, and effective immune responses, providing a potential solution. However, their practical application is hindered by low immunogenicity and short-term effectiveness. In this study, multiple linear epitopes from the conserved stem domain of hemagglutinin (HA2) and the ectodomain of matrix protein 2 (M2e) are combined with the Helicobacter pylori ferritin, a stable self-assembled nanoplatform, to develop an influenza multiepitope nanovaccine, named MHF. MHF is prokaryotically expressed in a soluble form and self-assembles into uniform nanoparticles. The subcutaneous immunization of mice with adjuvanted MHF induces cross-reactive neutralizing antibodies, ADCC, and cellular immunity, offering complete protection against H3N2 as well as partial protection against H1N1. Importantly, the vaccine cargo delivered by ferritin triggers epitope-specific memory B-cell responses, with antibody level persisting for over six months post-immunization. These findings indicate that self-assembled multiepitope nanovaccines elicit potent and long-lasting immune responses while significantly reducing the risk of vaccine escape mutants, and offer greater practicality in terms of scalable manufacturing and genetic manipulability, presenting a promising and effective strategy for future vaccine development. This article is protected by copyright. All rights reserved.
Keywords: HA2; M2e; Self-assembled ferritin; influenza A virus; long-lasting cross-protection; multiepitope nanovaccine.
. 2023 Nov 20:e2303531.
doi: 10.1002/adhm.202303531. Online ahead of print. Self-Assembled Multiepitope Nanovaccine Provides Long-Lasting Cross-Protection Against Influenza Virus
Jiaojiao Nie[SUP] 1 2 [/SUP], Qingyu Wang[SUP] 1 [/SUP], Chenxi Li[SUP] 1 [/SUP], Yongfei Zhou[SUP] 1 [/SUP], Xin Yao[SUP] 1 [/SUP], Lipeng Xu[SUP] 1 [/SUP], Yaotian Chang[SUP] 1 [/SUP], Fan Ding[SUP] 1 [/SUP], Lulu Sun[SUP] 1 [/SUP], Li Zhan[SUP] 1 [/SUP], Lvzhou Zhu[SUP] 1 [/SUP], Kunpeng Xie[SUP] 1 [/SUP], Xu Wang[SUP] 1 [/SUP], Yuhua Shi[SUP] 1 [/SUP], Qi Zhao[SUP] 2 3 [/SUP], Yaming Shan[SUP] 1 4 [/SUP]
Affiliations
- PMID: 37983728
- DOI: 10.1002/adhm.202303531
Seasonal influenza vaccines typically provide strain-specific protection and are reformulated annually, which is a complex and time-consuming process. Multiepitope vaccines, combining multiple conserved antigenic epitopes from a pathogen, can trigger more robust, diverse, and effective immune responses, providing a potential solution. However, their practical application is hindered by low immunogenicity and short-term effectiveness. In this study, multiple linear epitopes from the conserved stem domain of hemagglutinin (HA2) and the ectodomain of matrix protein 2 (M2e) are combined with the Helicobacter pylori ferritin, a stable self-assembled nanoplatform, to develop an influenza multiepitope nanovaccine, named MHF. MHF is prokaryotically expressed in a soluble form and self-assembles into uniform nanoparticles. The subcutaneous immunization of mice with adjuvanted MHF induces cross-reactive neutralizing antibodies, ADCC, and cellular immunity, offering complete protection against H3N2 as well as partial protection against H1N1. Importantly, the vaccine cargo delivered by ferritin triggers epitope-specific memory B-cell responses, with antibody level persisting for over six months post-immunization. These findings indicate that self-assembled multiepitope nanovaccines elicit potent and long-lasting immune responses while significantly reducing the risk of vaccine escape mutants, and offer greater practicality in terms of scalable manufacturing and genetic manipulability, presenting a promising and effective strategy for future vaccine development. This article is protected by copyright. All rights reserved.
Keywords: HA2; M2e; Self-assembled ferritin; influenza A virus; long-lasting cross-protection; multiepitope nanovaccine.