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

1
Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia
2
Department of Virology, Institute of Experimental Medicine, Saint Petersburg 197376, Russia
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(2), 197; https://doi.org/10.3390/vaccines8020197
Received: 30 March 2020 / Revised: 17 April 2020 / Accepted: 21 April 2020 / Published: 24 April 2020
(This article belongs to the Section Influenza Virus Vaccines)
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. View Full-Text
Keywords: influenza; conserved antigens; hemagglutinin stalk; M2e protein; virus-like particles; protection; vaccines influenza; conserved antigens; hemagglutinin stalk; M2e protein; virus-like particles; protection; vaccines
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Kirsteina, A.; Akopjana, I.; Bogans, J.; Lieknina, I.; Jansons, J.; Skrastina, D.; Kazaka, T.; Tars, K.; Isakova-Sivak, I.; Mezhenskaya, D.; Kotomina, T.; Matyushenko, V.; Rudenko, L.; Kazaks, A. Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens. Vaccines 2020, 8, 197.

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