{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T11:25:30Z","timestamp":1778757930295,"version":"3.51.4"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza hemagglutinin (HA) is considered a major protective antigen of seasonal influenza vaccine but antigenic drift of HA necessitates annual immunizations using new circulating HA versions. Low variation found within conserved non-HA influenza virus (INFV) antigens may maintain protection with less frequent immunizations. Conserved antigens of influenza A virus (INFV A) that can generate cross protection against multiple INFV strains were evaluated in BALB\/c mice using modified Vaccinia virus Ankara (MVA)-vectored vaccines that expressed INFV A antigens hemagglutinin (HA), matrix protein 1 (M1), nucleoprotein (NP), matrix protein 2 (M2), repeats of the external portion of M2 (M2e) or as tandem repeats (METR), and M2e with transmembrane region and cytoplasmic loop (M2eTML). Protection by combinations of non-HA antigens was equivalent to that of subtype-matched HA. Combinations of NP and forms of M2e generated serum antibody responses and protected mice against lethal INFV A challenge using PR8, pandemic H1N1 A\/Mexico\/4108\/2009 (pH1N1) or H5N1 A\/Vietnam\/1203\/2004 (H5N1) viruses, as demonstrated by reduced lung viral burden and protection against weight loss. The highest levels of protection were obtained with NP and M2e antigens delivered as MVA inserts, resulting in broadly protective immunity in mice and enhancement of previous natural immunity to INFV A.<\/jats:p>","DOI":"10.3390\/v13091708","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T03:13:17Z","timestamp":1630465997000},"page":"1708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Influenza Antigens NP and M2 Confer Cross Protection to BALB\/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses"],"prefix":"10.3390","volume":"13","author":[{"given":"Nutan","family":"Mytle","sequence":"first","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"},{"name":"Biomedical Advanced Research and Development Agency, U.S. Department of Health and Human Services, Washington, DC 20201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Leyrer","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"},{"name":"Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon R.","family":"Inglefield","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"},{"name":"Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea M.","family":"Harris","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"},{"name":"National Cancer Institute, National Institutes of Health, Frederick, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Minang","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"},{"name":"Optimal Health Care, 11377 Robinwood Dr, Hagerstown, MD 21742, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Lu","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhidong","family":"Ma","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hann\u00e9","family":"Andersen","sequence":"additional","affiliation":[{"name":"BIOQUAL, Inc., 12301 Parklawn Dr, Rockville, MD 20852, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan D.","family":"Grubaugh","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"},{"name":"Yale School of Public Health, Yale University, 60 College Street, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Guina","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"},{"name":"AstraZeneca, Gaithersburg, MD 20878, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario H.","family":"Skiadopoulos","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"},{"name":"U.S. Department of Health and Human Services, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-2176","authenticated-orcid":false,"given":"Michael J.","family":"Lacy","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1073\/pnas.90.9.4171","article-title":"Rates of spontaneous mutation among RNA viruses","volume":"90","author":"Drake","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1473-3099(11)70295-X","article-title":"Efficacy and effectiveness of influenza vaccines: A systematic review and meta-analysis","volume":"12","author":"Osterholm","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1093\/cid\/cir693","article-title":"Revisiting the 1976 \"swine flu\" vaccine clinical trials: Cross-reactive hemagglutinin and neuraminidase antibodies and their role in protection against the 2009 H1N1 pandemic virus in mice","volume":"53","author":"Xie","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"958","DOI":"10.4161\/cc.9.5.10913","article-title":"Genomic analysis of pandemic (H1N1) 2009 reveals association of increasing disease severity with emergence of novel hemagglutinin mutations","volume":"9","author":"Glinsky","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1023\/A:1008131312306","article-title":"Genomic analysis of matrix gene and antigenic studies of its gene product (M1) of a swine influenza virus (H1N1) causing chronic respiratory disease in pigs","volume":"21","author":"Welman","year":"2000","journal-title":"Virus Genes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1128\/jvi.66.2.1129-1138.1992","article-title":"Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts","volume":"66","author":"Bean","year":"1992","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1128\/jvi.67.5.2723-2729.1993","article-title":"Analysis of the evolution and variation of the human influenza A virus nucleoprotein gene from 1933 to 1990","volume":"67","author":"Shu","year":"1993","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"569","DOI":"10.3201\/eid1204.051020","article-title":"Prospects for universal influenza virus vaccine","volume":"12","author":"Gerhard","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.3390\/v6051974","article-title":"Universal influenza vaccines, a dream to be realized soon","volume":"6","author":"Zhang","year":"2014","journal-title":"Viruses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.7774\/cevr.2014.3.1.12","article-title":"New vaccines against influenza virus","volume":"3","author":"Lee","year":"2014","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1093\/bioinformatics\/btt304","article-title":"EpiCombFlu: Exploring known influenza epitopes and their combination to design a universal influenza vaccine","volume":"29","author":"Jaiswal","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.4161\/hv.25598","article-title":"Universal H1N1 influenza vaccine development: Identification of consensus class II hemagglutinin and neuraminidase epitopes derived from strains circulating between 1980 and 2011","volume":"9","author":"Moise","year":"2013","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.cmi.2017.02.009","article-title":"Universal influenza virus vaccines and therapeutic antibodies","volume":"23","author":"Nachbagauer","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.3390\/v6072735","article-title":"Modified vaccinia virus ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases","volume":"6","author":"Altenburg","year":"2014","journal-title":"Viruses"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/bs.aivir.2016.07.001","article-title":"Modified vaccinia virus ankara: History, Value in basic research, and current perspectives for vaccine development","volume":"97","author":"Volz","year":"2017","journal-title":"Adv. Virus Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1016\/j.vaccine.2015.04.086","article-title":"Market implementation of the MVA platform for pre-pandemic and pandemic influenza vaccines: A quantitative key opinion leader analysis","volume":"33","author":"Ramezanpour","year":"2015","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/srep01443","article-title":"Immunity against heterosubtypic influenza virus induced by adenovirus and MVA expressing nucleoprotein and matrix protein-1","volume":"3","author":"Lambe","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hessel, A., Savidis-Dacho, H., Coulibaly, S., Portsmouth, D., Kreil, T.R., Crowe, B.A., Schwendinger, M.G., Pilz, A., Barrett, P.N., and Falkner, F.G. (2014). MVA vectors expressing conserved influenza proteins protect mice against lethal challenge with H5N1, H9N2 and H7N1 viruses. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088340"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.vaccine.2013.01.038","article-title":"Cross-protective immunity against multiple influenza virus subtypes by a novel modified vaccinia Ankara (MVA) vectored vaccine in mice","volume":"31","author":"Brewoo","year":"2013","journal-title":"Vaccine"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Antrobus, R.D., Lillie, P.J., Berthoud, T.K., Spencer, A.J., McLaren, J.E., Ladell, K., Lambe, T., Milicic, A., Price, D.A., and Hill, A.V. (2012). A T cell-inducing influenza vaccine for the elderly: Safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048322"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/cid\/cis327","article-title":"Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans","volume":"55","author":"Lillie","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Folegatti, P.M., Bellamy, D., Flaxman, A., Mair, C., Ellis, C., Ramon, R.L., Ramos Lopez, F., Mitton, C., Baker, M., and Poulton, I. (2019). Safety and immunogenicity of the heterosubtypic influenza a vaccine MVA-NP+M1 manufactured on the AGE1.CR.pIX avian cell line. Vaccines, 7.","DOI":"10.3390\/vaccines7010033"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Prabakaran, M., Leyrer, S., He, F., Auer, S., Kumar, S.R., Kindsmueller, K., Mytle, N., Schneider, J., Lockhart, S., and Kwang, J. (2014). Progress toward a universal H5N1 vaccine: A recombinant modified vaccinia virus Ankara-expressing trivalent hemagglutinin vaccine. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107316"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0092-8674(88)90514-4","article-title":"Enhanced recognition of a modified peptide antigen by cytotoxic T cells specific for influenza nucleoprotein","volume":"52","author":"Bodmer","year":"1988","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/BF00346521","article-title":"Class I MHC molecules rather than other mouse genes dictate influenza epitope recognition by cytotoxic T cells","volume":"26","author":"Taylor","year":"1987","journal-title":"Immunogenetics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.4049\/jimmunol.143.9.3007","article-title":"Identification and characterization of T helper epitopes in the nucleoprotein of influenza A virus","volume":"143","author":"Gao","year":"1989","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/BF00172063","article-title":"MHC ligands and peptide motifs: First listing","volume":"41","author":"Rammensee","year":"1995","journal-title":"Immunogenetics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6318","DOI":"10.1128\/JVI.00427-06","article-title":"Poxvirus CD8+ T-cell determinants and cross-reactivity in BALB\/c mice","volume":"80","author":"Tscharke","year":"2006","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Vitelli, A., Quirion, M.R., Lo, C.Y., Misplon, J.A., Grabowska, A.K., Pierantoni, A., Ammendola, V., Price, G.E., Soboleski, M.R., and Cortese, R. (2013). Vaccination to conserved influenza antigens in mice using a novel Simian adenovirus vector, PanAd3, derived from the bonobo Pan paniscus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055435"},{"key":"ref_31","first-page":"3478","article-title":"Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals","volume":"118","author":"Lee","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6527","DOI":"10.1016\/j.vaccine.2012.08.054","article-title":"Enhanced immune response induced by a potential influenza A vaccine based on branched M2e polypeptides linked to tuftsin","volume":"30","author":"Liu","year":"2012","journal-title":"Vaccine"},{"key":"ref_33","first-page":"686549","article-title":"Virus-like particles containing the tetrameric ectodomain of influenza matrix protein 2 and flagellin induce heterosubtypic protection in mice","volume":"2013","author":"Wang","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.virol.2017.06.001","article-title":"Protein nanoparticle vaccine based on flagellin carrier fused to influenza conserved epitopes confers full protection against influenza a virus challenge","volume":"509","author":"Deng","year":"2017","journal-title":"Virology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.antiviral.2013.06.010","article-title":"Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza a virus infection","volume":"99","author":"Kim","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.nano.2013.08.005","article-title":"Nanoclusters self-assembled from conformation-stabilized influenza M2e as broadly cross-protective influenza vaccines","volume":"10","author":"Wang","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, W., Huang, B., Jiang, T., Wang, X., Qi, X., Gao, Y., Tan, W., and Ruan, L. (2012). Robust immunity and heterologous protection against influenza in mice elicited by a novel recombinant NP-M2e fusion protein expressed in E. coli. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052488"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jviromet.2008.08.011","article-title":"Immunization with plasmid DNA encoding influenza A virus nucleoprotein fused to a tissue plasminogen activator signal sequence elicits strong immune responses and protection against H5N1 challenge in mice","volume":"154","author":"Luo","year":"2008","journal-title":"J. Virol. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6845","DOI":"10.1016\/j.vaccine.2007.07.035","article-title":"Partial protection against H5N1 influenza in mice with a single dose of a chimpanzee adenovirus vector expressing nucleoprotein","volume":"25","author":"Roy","year":"2007","journal-title":"Vaccine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/1743-422X-9-322","article-title":"Influenza a virus nucleoprotein derived from Escherichia coli or recombinant vaccinia (Tiantan) virus elicits robust cross-protection in mice","volume":"9","author":"Huang","year":"2012","journal-title":"Virol. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5985","DOI":"10.1128\/JVI.00120-13","article-title":"Single-dose vaccination of a recombinant parainfluenza virus 5 expressing NP from H5N1 virus provides broad immunity against influenza A viruses","volume":"87","author":"Li","year":"2013","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kim, S.H., Kim, J.Y., Choi, Y., Nguyen, H.H., Song, M.K., and Chang, J. (2013). Mucosal vaccination with recombinant adenovirus encoding nucleoprotein provides potent protection against influenza virus infection. PLoS ONE, 8.","DOI":"10.1371\/annotation\/c2c0b5cc-ce3e-4c1f-a821-caed5697d72d"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1016\/j.vaccine.2005.04.047","article-title":"Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein","volume":"23","author":"Epstein","year":"2005","journal-title":"Vaccine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1128\/jvi.68.6.3505-3511.1994","article-title":"Primary pulmonary cytotoxic T lymphocytes induced by immunization with a vaccinia virus recombinant expressing influenza A virus nucleoprotein peptide do not protect mice against challenge","volume":"68","author":"Lawson","year":"1994","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.4049\/jimmunol.1003057","article-title":"Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus","volume":"186","author":"LaMere","year":"2011","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1084\/jem.20131692","article-title":"Prolonged antigen presentation by immune complex-binding dendritic cells programs the proliferative capacity of memory CD8 T cells","volume":"211","author":"Leon","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/0264-410X(94)00083-Y","article-title":"Intranasal immunization of mice against influenza with synthetic peptides anchored to proteosomes","volume":"13","author":"Levi","year":"1995","journal-title":"Vaccine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0165-2478(93)90105-B","article-title":"No recognition of MHC class II+ cells infected with a vaccinia virus encoding influenza type A nucleoprotein by class II-restricted T cells","volume":"36","author":"Freer","year":"1993","journal-title":"Immunol. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1046\/j.0019-2805.2001.01357.x","article-title":"Immunization onto bare skin with synthetic peptides: Immunomodulation with a CpG-containing oligodeoxynucleotide and effective priming of influenza virus-specific CD4+ T cells","volume":"105","author":"Beignon","year":"2002","journal-title":"Immunology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/jmv.23812","article-title":"Identification of a highly conserved and surface exposed B-cell epitope on the nucleoprotein of influenza A virus","volume":"86","author":"Gui","year":"2014","journal-title":"J. Med. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jviromet.2007.09.016","article-title":"Development and application of monoclonal antibodies against avian influenza virus nucleoprotein","volume":"147","author":"Yang","year":"2008","journal-title":"J. Virol. Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.imlet.2004.03.003","article-title":"Monoclonal antibodies recognizing EVETPIRN epitope of influenza A virus M2 protein could protect mice from lethal influenza A virus challenge","volume":"93","author":"Liu","year":"2004","journal-title":"Immunol. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1574-695X.2008.00402.x","article-title":"Fine-epitope mapping of an antibody that binds the ectodomain of influenza matrix protein 2","volume":"53","author":"Zou","year":"2008","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.vaccine.2007.10.062","article-title":"Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin","volume":"26","author":"Huleatt","year":"2008","journal-title":"Vaccine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1128\/jvi.65.10.5491-5498.1991","article-title":"Evolutionary analysis of the influenza A virus M gene with comparison of the M1 and M2 proteins","volume":"65","author":"Ito","year":"1991","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zinder, D., Bedford, T., Gupta, S., and Pascual, M. (2013). The roles of competition and mutation in shaping antigenic and genetic diversity in influenza. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003104"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/9\/1708\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:54:04Z","timestamp":1760165644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/9\/1708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,27]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["v13091708"],"URL":"https:\/\/doi.org\/10.3390\/v13091708","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,27]]}}}