{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:41:01Z","timestamp":1775911261784,"version":"3.50.1"},"reference-count":23,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development (AMED)","award":["JP20jm0210054h0004"],"award-info":[{"award-number":["JP20jm0210054h0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to develop a new vaccine in the case of an H4 influenza virus infection in humans, considering that this virus has a different antigenicity from seasonal human influenza viruses. In this study, after selecting vaccine candidate strains based on their antigenic relation to one of the pig isolates, A\/swine\/Missouri\/A01727926\/2015 (H4N6) (MO\/15), an inactivated whole-particle vaccine was prepared from A\/swan\/Hokkaido\/481102\/2017 (H4N6). This vaccine showed high immunogenicity in mice, and the antibody induced by the vaccine showed high cross-reactivity to the MO\/15 virus. This vaccine induced sufficient neutralizing antibodies and mitigated the effects of an MO\/15 infection in a mouse model. This study is the first to suggest that an inactivated whole-particle vaccine prepared from an influenza virus isolated from wild birds is an effective countermeasure in case of a future influenza pandemic caused by the H4 influenza virus.<\/jats:p>","DOI":"10.3390\/vaccines8040768","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T09:21:15Z","timestamp":1608110475000},"page":"768","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Potency of an Inactivated Influenza Vaccine against a Challenge with A\/Swine\/Missouri\/A01727926\/2015 (H4N6) in Mice for Pandemic Preparedness"],"prefix":"10.3390","volume":"8","author":[{"given":"Hirotaka","family":"Hayashi","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-Ku, Sapporo 060-0818, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norikazu","family":"Isoda","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-Ku, Sapporo 060-0818, Japan"},{"name":"International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enkhbold","family":"Bazarragchaa","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-Ku, Sapporo 060-0818, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Nomura","sequence":"additional","affiliation":[{"name":"Laboratory of Biologics Development, Research Center for Zoonosis Control, Hokkaido University, Kita 20 Nishi 10, Kita-Ku, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-6526","authenticated-orcid":false,"given":"Keita","family":"Matsuno","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-Ku, Sapporo 060-0818, Japan"},{"name":"International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Okamatsu","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-Ku, Sapporo 060-0818, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kida","sequence":"additional","affiliation":[{"name":"Research Center for Zoonosis Control, Hokkaido University, Kita 20 Nishi 10, Kita-Ku, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-1688","authenticated-orcid":false,"given":"Yoshihiro","family":"Sakoda","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-Ku, Sapporo 060-0818, Japan"},{"name":"International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"ref_1","first-page":"650","article-title":"Orthomyxoriruses","volume":"Volume 1","author":"Whelan","year":"2020","journal-title":"Fields Virology: Emerging Viruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0168-1702(93)90056-S","article-title":"Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium","volume":"29","author":"Couceiro","year":"1993","journal-title":"Virus Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0042-6822(87)90353-9","article-title":"Antigenic and genetic conservation of H3 influenza virus in wild ducks","volume":"159","author":"Kida","year":"1987","journal-title":"Virology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nakayama, M., Shichinohe, S., Itoh, Y., Ishigaki, H., Kitano, M., Arikata, M., Pham, V.L., Ishida, H., Kitagawa, N., and Okamatsu, M. (2013). Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082740"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1292\/jvms.11-0471","article-title":"An H9N2 infuenza virus vaccine prepared from a non-pathogenic isolate from a migratory duck confers protective immunity in mice against challenge with an H9N2 virus isolated from a girl in Hong Kong","volume":"74","author":"Nomura","year":"2012","journal-title":"J. Vet. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1743-422X-10-47","article-title":"Potency of a vaccine prepared from A\/swine\/Hokkaido\/2\/1981 (H1N1) against A\/Narita\/1\/2009 (H1N1) pandemic influenza virus strain","volume":"10","author":"Okamatsu","year":"2013","journal-title":"Virol. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.celrep.2017.07.028","article-title":"Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4","volume":"20","author":"Song","year":"2017","journal-title":"Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9322","DOI":"10.1128\/JVI.74.19.9322-9327.2000","article-title":"Isolation and Characterization of H4N6 Avian Influenza Viruses from Pigs with Pneumonia in Canada","volume":"74","author":"Karasin","year":"2000","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13879","DOI":"10.1128\/JVI.02726-12","article-title":"Complete Genome Sequence of a Novel H4N1 Influenza Virus Isolated from a Pig in Central China","volume":"86","author":"Hu","year":"2012","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9542","DOI":"10.1128\/JVI.01475-12","article-title":"Complete Genome Sequence of an Avian-Like H4N8 Swine Influenza Virus Discovered in Southern China","volume":"86","author":"Su","year":"2012","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.virol.2017.08.021","article-title":"Detection and characterization of an H4N6 avian-lineage influenza A virus in pigs in the Midwestern United States","volume":"511","author":"Abente","year":"2017","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e04068","DOI":"10.1016\/j.heliyon.2020.e04068","article-title":"Molecular characterization and three-dimensional structures of avian H8, H11, H14, H15 and swine H4 influenza virus hemagglutinins","volume":"6","author":"Yang","year":"2020","journal-title":"Heliyon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1080\/17476348.2019.1645011","article-title":"The risk of a swine influenza pandemic: Still a concern?","volume":"13","author":"Loubet","year":"2019","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1126\/science.1097211","article-title":"Mapping the Antigenic and Genetic","volume":"305","author":"Smith","year":"2004","journal-title":"Science"},{"key":"ref_15","unstructured":"World Organisation for Animal Health (2020, December 06). Avian Influenza (Infection with Avian Influenza Viruses). Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Available online: https:\/\/www.oie.int\/standard-setting\/terrestrial-manual\/access-online\/."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1126\/science.aac5017","article-title":"Dengue viruses cluster antigenically but not as discrete serotypes","volume":"349","author":"Katzelnick","year":"2016","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/0042-6822(82)90375-0","article-title":"Biological activity of monoclonal antibodies to operationally defined antigenic regions on the hemagglutinin molecule of A\/Seal\/Massachusetts\/1\/80 (H7N7) influenza virus","volume":"122","author":"Kida","year":"1982","journal-title":"Virology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/nmeth.3663","article-title":"ANOVA and the analysis of drug combination experiments","volume":"12","author":"Ashton","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1128\/JVI.02692-15","article-title":"Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China","volume":"90","author":"Liang","year":"2016","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00847-20","DOI":"10.1128\/JVI.00847-20","article-title":"Tissue tropisms of avian influenza A viruses affect their spillovers from wild birds to pigs","volume":"94","author":"Zhang","year":"2020","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17204","DOI":"10.1073\/pnas.1921186117","article-title":"Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection","volume":"117","author":"Sun","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shin, D., Yang, W., Peng, J., Sawatsky, B., and Messling, V. (2020). Von Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation. Viruses, 12.","DOI":"10.3390\/v12060589"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1637\/11086-041015-RegR","article-title":"Antigenic Characterization of H3 Subtypes of Avian Influenza A Viruses from North America","volume":"60","author":"Bailey","year":"2016","journal-title":"Avian Dis."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/768\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:45:43Z","timestamp":1760179543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,16]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["vaccines8040768"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8040768","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,16]]}}}