Abstract
Universal influenza virus vaccine candidates that focus on the conserved hemagglutinin (HA) stalk domain and the extracellular domain of the matrix protein 2 (M2e) have been developed to increase the breadth of protection against multiple strains. In this study, we report a novel inactivated influenza virus vaccine approach that combines these two strategies. We inserted a human consensus M2e epitope into the immunodominant antigenic site (Ca2 site) of three different chimeric HAs (cHAs). Sequential immunization with inactivated viruses containing these modified cHAs substantially enhanced M2e antibody responses while simultaneously boosting stalk antibody responses. The combination of additional M2e antibodies with HA stalk antibodies resulted in superior antibody-mediated protection in mice against challenge viruses expressing homologous or heterosubtypic hemagglutinin and neuraminidase compared to vaccination strategies that targeted the HA stalk or M2e epitopes in isolation.
Highlights
IntroductionThe matrix protein 2 (M2) of influenza A viruses is a tetrameric type III integral transmembrane protein comprised of an N-terminal ectodomain (M2e, aa 1–24), a transmembrane domain (aa 25–44)
The matrix protein 2 (M2) of influenza A viruses is a tetrameric type III integral transmembrane protein comprised of an N-terminal ectodomain (M2e, aa 1–24), a transmembrane domainand a C-terminal cytoplasmic tail [1]
To overcome the poor immunogenicity of the M2 protein in the inactivated influenza virus vaccine (IIV) platform, we aimed to improve the antigenic visibility of the M2e by grafting the consensus epitope into one of the major antigenic sites of H1 hemagglutinin (Sa, Sb, Ca1, Ca2 or Cb)
Summary
The matrix protein 2 (M2) of influenza A viruses is a tetrameric type III integral transmembrane protein comprised of an N-terminal ectodomain (M2e, aa 1–24), a transmembrane domain (aa 25–44). A C-terminal cytoplasmic tail (aa 45–97) [1]. It is expressed from the spliced mRNA of the M segment [2,3], and it has been reported to play important roles in virus entry and egression [4]. After the virus is endocytosed, the ion channel activity of the M2 proteins allows for the acidification of the virion interior within the endosomes, resulting in disassembly of the viral particles and release of the viral genomic segments. In contrast to the other two surface glycoproteins of the virion—hemagglutinin (HA)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
