Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens.
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.
['Kirsteina|Anna|A|', 'Akopjana|Inara|I|', 'Bogans|Janis|J|', 'Lieknina|Ilva|I|', 'Jansons|Juris|J|', 'Skrastina|Dace|D|', 'Kazaka|Tatjana|T|', 'Tars|Kaspars|K|', 'Isakova-Sivak|Irina|I|', 'Mezhenskaya|Daria|D|', 'Kotomina|Tatiana|T|', 'Matyushenko|Victoria|V|', 'Rudenko|Larisa|L|', 'Kazaks|Andris|A|']
vaccines influenza hemagglutinin stalk protection virus-like particles M2e protein conserved antigens