{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:22:56Z","timestamp":1785363776884,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["1.1.1.1\/16\/A\/054"],"award-info":[{"award-number":["1.1.1.1\/16\/A\/054"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/vaccines8020197","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T11:42:14Z","timestamp":1587728534000},"page":"197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens"],"prefix":"10.3390","volume":"8","author":[{"given":"Anna","family":"Kirsteina","sequence":"first","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inara","family":"Akopjana","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Bogans","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilva","family":"Lieknina","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-4392","authenticated-orcid":false,"given":"Juris","family":"Jansons","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dace","family":"Skrastina","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Kazaka","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaspars","family":"Tars","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2801-1508","authenticated-orcid":false,"given":"Irina","family":"Isakova-Sivak","sequence":"additional","affiliation":[{"name":"Department of Virology, Institute of Experimental Medicine, Saint Petersburg 197376, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-7682","authenticated-orcid":false,"given":"Daria","family":"Mezhenskaya","sequence":"additional","affiliation":[{"name":"Department of Virology, Institute of Experimental Medicine, Saint Petersburg 197376, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Kotomina","sequence":"additional","affiliation":[{"name":"Department of Virology, Institute of Experimental Medicine, Saint Petersburg 197376, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Matyushenko","sequence":"additional","affiliation":[{"name":"Department of Virology, Institute of Experimental Medicine, Saint Petersburg 197376, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Rudenko","sequence":"additional","affiliation":[{"name":"Department of Virology, Institute of Experimental Medicine, Saint Petersburg 197376, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andris","family":"Kazaks","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020, March 06). 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