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Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens

tetano

Editor, Senior Moderator
Vaccines (Basel). 2020 Apr 24;8(2). pii: E197. doi: 10.3390/vaccines8020197.
Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens.


Kirsteina A[SUP]1[/SUP], Akopjana I[SUP]1[/SUP], Bogans J[SUP]1[/SUP], Lieknina I[SUP]1[/SUP], Jansons J[SUP]1[/SUP], Skrastina D[SUP]1[/SUP], Kazaka T[SUP]1[/SUP], Tars K[SUP]1[/SUP], Isakova-Sivak I[SUP]2[/SUP], Mezhenskaya D[SUP]2[/SUP], Kotomina T[SUP]2[/SUP], Matyushenko V[SUP]2[/SUP], Rudenko L[SUP]2[/SUP], Kazaks A[SUP]1[/SUP].

Author information




Abstract

Influenza, an acute, highly contagious respiratory disease, remains a significant threat to public health. More effective vaccination strategies aimed at inducing broad cross-protection not only against seasonal influenza variants, but also zoonotic and emerging pandemic influenza strains are urgently needed. A number of conserved protein targets to elicit such cross-protective immunity have been under investigation, with long alpha-helix (LAH) from hemagglutinin stalk and ectodomain of matrix protein 2 ion channel (M2e) being the most studied ones. Recently, we have reported the three-dimensional structure and some practical applications of LAH expressed in Escherichia coli system (referred to as tri-stalk protein). In the present study, we investigated the immunogenicity and efficacy of a panel of broadly protective influenza vaccine prototypes based on both influenza tri-stalk and triple M2e (3M2e) antigens integrated into phage AP205 virus-like particles (VLPs). While VLPs containing the 3M2e alone induced protection against standard homologous and heterologous virus challenge in mice, only the combination of both conserved influenza antigens into a single VLP fully protected mice from a high-dose homologous H1N1 influenza infection. We propose that a combination of genetic fusion and chemical coupling techniques to expose two different foreign influenza antigens on a single particle is a perspective approach for generation of a broadly-effective vaccine candidate that could protect against the constantly emerging influenza virus strains.



KEYWORDS:

M2e protein; conserved antigens; hemagglutinin stalk; influenza; protection; vaccines; virus-like particles


PMID:32344753DOI:10.3390/vaccines8020197
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