{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:29:05Z","timestamp":1777577345617,"version":"3.51.4"},"reference-count":87,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Food and Agriculture","award":["2017-67015-32034"],"award-info":[{"award-number":["2017-67015-32034"]}]},{"name":"National Institute of Food and Agriculture","award":["2022-67015-36349"],"award-info":[{"award-number":["2022-67015-36349"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza A viruses (IAV-S) belonging to the H1 subtype are endemic in swine worldwide. Antigenic drift and antigenic shift lead to a substantial antigenic diversity in circulating IAV-S strains. As a result, the most commonly used vaccines based on whole inactivated viruses (WIVs) provide low protection against divergent H1 strains due to the mismatch between the vaccine virus strain and the circulating one. Here, a consensus coding sequence of the full-length of HA from H1 subtype was generated in silico after alignment of the sequences from IAV-S isolates obtained from public databases and was delivered to pigs using the Orf virus (ORFV) vector platform. The immunogenicity and protective efficacy of the resulting ORFV\u0394121conH1 recombinant virus were evaluated against divergent IAV-S strains in piglets. Virus shedding after intranasal\/intratracheal challenge with two IAV-S strains was assessed by real-time RT-PCR and virus titration. Viral genome copies and infectious virus load were reduced in nasal secretions of immunized animals. Flow cytometry analysis showed that the frequency of T helper\/memory cells, as well as cytotoxic T lymphocytes (CTLs), were significantly higher in the peripheral blood mononuclear cells (PBMCs) of the vaccinated groups compared to unvaccinated animals when they were challenged with a pandemic strain of IAV H1N1 (CA\/09). Interestingly, the percentage of T cells was higher in the bronchoalveolar lavage of vaccinated animals in relation to unvaccinated animals in the groups challenged with a H1N1 from the gamma clade (OH\/07). In summary, delivery of the consensus HA from the H1 IAV-S subtype by the parapoxvirus ORFV vector decreased shedding of infectious virus and viral load of IAV-S in nasal secretions and induced cellular protective immunity against divergent influenza viruses in swine.<\/jats:p>","DOI":"10.3390\/v15040994","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T03:20:39Z","timestamp":1681874439000},"page":"994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["An Orf-Virus (ORFV)-Based Vector Expressing a Consensus H1 Hemagglutinin Provides Protection against Diverse Swine Influenza Viruses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-1055","authenticated-orcid":false,"given":"Gabriela Mansano","family":"do Nascimento","sequence":"first","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina","family":"Bugybayeva","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Center for Food Animal Health, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veerupaxagouda","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Center for Food Animal Health, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Schrock","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Center for Food Animal Health, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganesh","family":"Yadagiri","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Center for Food Animal Health, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gourapura J.","family":"Renukaradhya","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Center for Food Animal Health, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3237-8940","authenticated-orcid":false,"given":"Diego G.","family":"Diel","sequence":"additional","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.vetmic.2017.10.016","article-title":"Molecular epidemiology of swine influenza A viruses in the Southeastern United States, highlights regional differences in circulating strains","volume":"211","author":"Kyriakis","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.virol.2018.02.006","article-title":"Antigenic and genetic evolution of contemporary swine H1 influenza viruses in the United States","volume":"518","author":"Rajao","year":"2018","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/irv.12610","article-title":"Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012 to 2016","volume":"13","author":"Bolton","year":"2019","journal-title":"Influenza Other Respi. Viruses"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Sun, F., Li, L., Chen, T., Cao, S., Ding, G., Cong, F., Liu, J., Qin, L., and Liu, S. (2020). Evolution and pathogenicity of the H1 and H3 subtypes of swine influenza virus in mice between 2016 and 2019 in China. Viruses, 12.","DOI":"10.3390\/v12030298"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8243","DOI":"10.1128\/JVI.74.18.8243-8251.2000","article-title":"Evolution of Swine H3N2 Influenza Viruses in the United States","volume":"74","author":"Webby","year":"2000","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9920","DOI":"10.1128\/JVI.00840-15","article-title":"Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013","volume":"89","author":"Watson","year":"2015","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12217","DOI":"10.7554\/eLife.12217","article-title":"The global antigenic diversity of swine influenza A viruses","volume":"5","author":"Lewis","year":"2016","journal-title":"Elife"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0378-1135(00)00165-6","article-title":"Emergence of H3N2 reassortant influenza A viruses in North American pigs","volume":"74","author":"Zhou","year":"2000","journal-title":"Vet. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1084\/jem.54.3.373","article-title":"From the Department of Animal Pathology of The Rockefeller Institute for Medical Description of filters","volume":"54","author":"Shope","year":"1931","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Richt, J.A., and Webby, R.J. (2013). History of Swine Influenza BT\u2014Swine Influenza, Springer.","DOI":"10.1007\/978-3-642-36871-4"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"198118","DOI":"10.1016\/j.virusres.2020.198118","article-title":"Swine influenza virus: Current status and challenge","volume":"288","author":"Ma","year":"2020","journal-title":"Virus Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1056\/NEJM197603252941308","article-title":"Isolation of swine influenza virus from autopsy lung tissue of man","volume":"294","author":"Smith","year":"1976","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40813-021-00196-0","article-title":"Current and prospective control strategies of influenza A virus in swine","volume":"7","author":"Salvesen","year":"2021","journal-title":"Porc. Health Manag."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.3201\/eid2510.190068","article-title":"Bidirectional Human\u2014Swine Transmission of seasonal influenza A (H1N1) Pdm09 virus in pig herd, France, 2018","volume":"25","author":"Chastagner","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11210","DOI":"10.1128\/JVI.01211-10","article-title":"Swine influenza H1N1 virus induces acute inflammatory immune responses in pig lungs: A potential animal model for human H1N1 influenza virus","volume":"84","author":"Khatri","year":"2010","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/infdis\/jiv399","article-title":"Evolutionary dynamics of influenza a viruses in US exhibition swine","volume":"213","author":"Nelson","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_17","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_18","unstructured":"Barr, J.N., and Fearns, R. (2016). Genome Stability from Virus to Humam Application, Academic Press."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41541-019-0147-z","article-title":"Pandemic influenza virus vaccines boost hemagglutinin stalk-specific antibody responses in primed adult and pediatric cohorts","volume":"4","author":"Nachbagauer","year":"2019","journal-title":"Npj Vaccines"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/S2095-3119(19)62579-7","article-title":"Identification of an H1N1 subtype of swine influenza virus and serological analysis","volume":"18","author":"Min","year":"2019","journal-title":"J. Integr. Agric."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3389\/fvets.2018.00347","article-title":"Adaptation of human influenza viruses to swine","volume":"5","author":"Rajao","year":"2019","journal-title":"Front. Vet. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7367","DOI":"10.1128\/JVI.72.9.7367-7373.1998","article-title":"Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential","volume":"72","author":"Ito","year":"1998","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000157337","article-title":"Pigs as \u2018Mixing Vessels\u2019 for the Creation of New Pandemic Influenza A Viruses","volume":"2","author":"Scholtissek","year":"1990","journal-title":"Med. Princ. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13538","DOI":"10.1073\/pnas.0806901105","article-title":"A consensus\u2014Hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses","volume":"105","author":"Chen","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3390\/vaccines3010022","article-title":"Optimal Use of Vaccines for Control of Influenza A Virus in Swine","volume":"3","author":"Sandbulte","year":"2015","journal-title":"Vaccines"},{"key":"ref_26","unstructured":"USDA (2018). Veterinary Biological Products: Licensees and Permittees, USDA APHIS Center for Veterinary Biologics."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1016\/j.vaccine.2019.02.078","article-title":"Vaccine-mediated protection of pigs against infection with pandemic H1N1 2009 swine influenza A virus requires a close antigenic match between the vaccine antigen and challenge virus","volume":"37","author":"Everett","year":"2019","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11009","DOI":"10.1128\/JVI.00787-06","article-title":"Vaccination of Pigs against Swine Influenza Viruses by Using an NS1-Truncated Modified Live-Virus Vaccine","volume":"80","author":"Richt","year":"2006","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.virusres.2004.02.023","article-title":"Genetic Relationships, Serological Cross-Reaction and Cross-Protection between H1N2 and Other Influenza a Virus Subtypes Endemic in European Pigs","volume":"103","author":"Brown","year":"2004","journal-title":"Virus Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1099\/0022-1317-82-11-2697","article-title":"Respiratory and systemic humoral and cellular immune responses of pigs to a heterosubtypic influenza A virus infection","volume":"82","author":"Heinen","year":"2001","journal-title":"J. Gen. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1086\/524988","article-title":"Swine Influenza Virus: Zoonotic Potential and Vaccination Strategies for the Control of Avian and Swine Influenzas","volume":"197","author":"Thacker","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/nbt.2436","article-title":"Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection","volume":"30","author":"Petsch","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_33","unstructured":"Kitikoon, P. (2007). Strategy to Improve Swine Influenza Virus (SIV) Vaccination, Iowa State University."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9400","DOI":"10.1128\/JVI.78.17.9400-9411.2004","article-title":"Immunomodulatory effects of inactivated parapoxvirus ovis (ORF virus) on human peripheral immune cells: Induction of cytokine secretion in monocytes and Th1-like cells","volume":"78","author":"Friebe","year":"2004","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5915","DOI":"10.1016\/j.vaccine.2007.05.035","article-title":"Efficient priming against classical swine fever with a safe glycoprotein E2 expressing Orf virus recombinant (ORFV VrV-E2)","volume":"25","author":"Voigt","year":"2007","journal-title":"Vaccine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1099\/jgv.0.000586","article-title":"Immunogenicity of a Recombinant Parapoxvirus Expressing the Spike Protein of Porcine Epidemic Diarrhea Virus","volume":"97","author":"Hain","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.3389\/fimmu.2021.747574","article-title":"Protective efficacy of an orf virus-vector encoding the hemagglutinin and the nucleoprotein of influenza A virus in swine","volume":"12","author":"Joshi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1007\/s00705-018-3855-1","article-title":"Passive immunity to porcine epidemic diarrhea virus following immunization of pregnant gilts with a recombinant orf virus vector expressing the spike protein","volume":"163","author":"Joshi","year":"2018","journal-title":"Arch. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1128\/JVI.78.1.168-177.2004","article-title":"Genomes of the parapoxviruses ORF virus and bovine papular stomatitis virus","volume":"78","author":"Delhon","year":"2004","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.virol.2017.08.027","article-title":"Immunogenicity of ORFV-based vectors expressing the rabies virus glycoprotein in livestock species","volume":"511","author":"Martins","year":"2017","journal-title":"Virology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1128\/JVI.02291-09","article-title":"A novel inhibitor of the NF-\u03baB signaling pathway encoded by the parapoxvirus orf virus","volume":"84","author":"Diel","year":"2010","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/JVI.01149-10","article-title":"A Nuclear Inhibitor of NF- B Encoded by a Poxvirus","volume":"85","author":"Diel","year":"2011","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1128\/JVI.02236-10","article-title":"Orf virus ORFV121 encodes a novel inhibitor of NF-kappaB that contributes to virus virulence","volume":"85","author":"Diel","year":"2011","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jviromet.2004.08.009","article-title":"A natural vaccinia virus promoter with exceptional capacity to direct protein synthesis","volume":"122","author":"Liu","year":"2004","journal-title":"J. Virol. Methods"},{"key":"ref_45","unstructured":"Mahy, B.W.J., and Kangro, H.O. (1996). Virology Methods Manual, Academic Press."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.vetmic.2009.04.028","article-title":"Characterization of triple reassortant H1N1 influenza A viruses from swine in Ohio","volume":"139","author":"Yassine","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1177\/0300985813513043","article-title":"Influenza A Virus Infections in Swine: Pathogenesis and Diagnosis","volume":"51","author":"Janke","year":"2014","journal-title":"Vet. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1089\/vim.2010.0051","article-title":"Porcine reproductive and respiratory syndrome virus-Induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigs","volume":"23","author":"Renukaradhya","year":"2010","journal-title":"Viral Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.3389\/fimmu.2019.01509","article-title":"Amish (rural) vs. Non-amish (urban) infant fecal microbiotas are highly diverse and their transplantation lead to differences in mucosal immune maturation in a humanized germfree piglet model","volume":"10","author":"Dhakal","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.jconrel.2016.12.039","article-title":"Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs","volume":"247","author":"Dhakal","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"596964","DOI":"10.3389\/fimmu.2020.596964","article-title":"Intranasal Delivery of Inactivated Influenza Virus and Poly(I:C) Adsorbed Corn-Based Nanoparticle Vaccine Elicited Robust Antigen-Specific Cell-Mediated Immune Responses in Maternal Antibody Positive Nursery Pigs","volume":"11","author":"Patil","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_52","unstructured":"(2023, March 10). Created with BioRender.com. Available online: https:\/\/www.biorender.com."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.1128\/JVI.76.11.5435-5451.2002","article-title":"Human Immunodeficiency Virus Type 1 Subtype C Molecular Phylogeny: Consensus Sequence for an AIDS Vaccine Design?","volume":"76","author":"Novitsky","year":"2002","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6745","DOI":"10.1128\/JVI.02484-05","article-title":"Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen","volume":"80","author":"Weaver","year":"2006","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6462","DOI":"10.1128\/JVI.00383-15","article-title":"Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost","volume":"89","author":"Hulot","year":"2015","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Webby, R.J., and Weaver, E.A. (2015). Centralized consensus hemagglutinin genes induce protective immunity against H1, H3 and H5 influenza viruses. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140702"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"38780","DOI":"10.18632\/oncotarget.16353","article-title":"A consensus-hemagglutinin-based vaccine delivered by an attenuated Salmonella mutant protects chickens against heterologous H7N1 influenza virus","volume":"8","author":"Hyoung","year":"2017","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14912","DOI":"10.1038\/s41598-017-14891-y","article-title":"Efficacy of an Adenoviral Vectored Multivalent Centralized Influenza Vaccine","volume":"7","author":"Lingel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.vaccine.2016.11.051","article-title":"Sequential immunization with consensus influenza hemagglutinins raises cross-reactive neutralizing antibodies against various heterologous HA strains","volume":"35","author":"Zhou","year":"2017","journal-title":"Vaccine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"108451","DOI":"10.1016\/j.vetmic.2019.108451","article-title":"Design and characterization of a consensus hemagglutinin vaccine immunogen against H3 influenza A viruses of swine","volume":"239","author":"Sun","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4049\/immunohorizons.1800044","article-title":"Elicitation of Broadly Protective Antibodies following Infection with Influenza Viruses Expressing H1N1 Computationally Optimized Broadly Reactive Hemagglutinin Antigens","volume":"2","author":"Sautto","year":"2018","journal-title":"ImmunoHorizons"},{"key":"ref_62","first-page":"767","article-title":"The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses","volume":"70","author":"Hobson","year":"1972","journal-title":"J. Hyg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1016\/j.vaccine.2007.01.063","article-title":"Immunogenicity of novel consensus-based DNA vaccines against avian influenza","volume":"25","author":"Laddy","year":"2007","journal-title":"Vaccine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/sj.mt.6300036","article-title":"Enhanced cellular immune responses elicited by an engineered HIV-1 subtype B consensus-based envelope DNA vaccine","volume":"15","author":"Yan","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1073\/pnas.0813390106","article-title":"Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-term persistence of protective antibody levels","volume":"106","author":"Galli","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.4049\/jimmunol.0801814","article-title":"Tc17, a Unique Subset of CD8 T Cells That Can Protect against Lethal Influenza Challenge","volume":"182","author":"Hamada","year":"2009","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/nm.2612","article-title":"Preexisting influenza-specific CD4 + T cells correlate with disease protection against influenza challenge in humans","volume":"18","author":"Wilkinson","year":"2012","journal-title":"Nat. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.vaccine.2006.08.036","article-title":"Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice","volume":"25","author":"Kreijtz","year":"2007","journal-title":"Vaccine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1128\/JVI.02508-09","article-title":"Cytotoxic T Cells Are the Predominant Players Providing Cross-Protective Immunity Induced by \u03b3-Irradiated Influenza A Viruses","volume":"84","author":"Furuya","year":"2010","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.4049\/jimmunol.172.4.2453","article-title":"Recognition of Homo- and Heterosubtypic Variants of Influenza A Viruses by Human CD8 + T Lymphocytes","volume":"172","author":"Boon","year":"2004","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1016\/j.vaccine.2010.08.067","article-title":"Impact of prior seasonal influenza vaccination and infection on pandemic A (H1N1) influenza virus replication in ferrets","volume":"29","author":"Ellebedy","year":"2011","journal-title":"Vaccine"},{"key":"ref_72","first-page":"847","article-title":"Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A\/H1N1 2009: Case-control study in Mexico City","volume":"339","year":"2009","journal-title":"BMJ"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/nm.3350","article-title":"Cellular immune correlates of protection against symptomatic pandemic influenza","volume":"19","author":"Sridhar","year":"2013","journal-title":"Nat. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1164\/rccm.201411-1988OC","article-title":"Natural T cell-mediated protection against seasonal and pandemic influenza: Results of the flu watch cohort study","volume":"191","author":"Hayward","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Brookes, S.M., N\u00fa\u00f1ez, A., Choudhury, B., Matrosovich, M., Essen, S.C., Clifford, D., Slomka, M.J., Kuntz-Simon, G., Garcon, F., and Nash, B. (2010). Replication, pathogenesis and transmission of pandemic (H1N1) 2009 virus in non-immune pigs. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009068"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"11626","DOI":"10.1128\/JVI.05705-11","article-title":"2009 Pandemic H1N1 Influenza Virus Causes Disease and Upregulation of Genes Related to Inflammatory and Immune Responses, Cell Death, and Lipid Metabolism in Pigs","volume":"85","author":"Ma","year":"2011","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nri3307","article-title":"Transcriptional control of effector and memory CD8+ T cell differentiation","volume":"12","author":"Kaech","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1084\/jem.20160938","article-title":"Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance","volume":"213","author":"Takamura","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1189\/jlb.0313180","article-title":"Lung-resident memory CD8 T cells (T RM) are indispensable for optimal cross-protection against pulmonary virus infection 2","volume":"95","author":"Wu","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"ref_80","first-page":"e85832","article-title":"Vaccine-generated lung tissue\u2013resident memory T cells provide heterosubtypic protection to influenza infection","volume":"1","author":"Zens","year":"2019","journal-title":"JCI Insight"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9312","DOI":"10.1128\/JVI.77.17.9312-9323.2003","article-title":"Novel recombinant parapoxvirus vectors induce protective humoral and cellular immunity against lethal herpesvirus challenge infection in mice","volume":"77","author":"Fischer","year":"2003","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0168-1656(99)00141-8","article-title":"Parapoxviruses: Potential alternative vectors for directing the immune response in permissive and non-permissive hosts","volume":"73","author":"Rziha","year":"1999","journal-title":"J. Biotechnol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Rohde, J., Amann, R., and Rziha, H.-J. (2013). New Orf virus (Parapoxvirus) recombinant expressing H5 hemagglutinin protects mice against H5N1 and H1N1 influenza A virus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083802"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5027","DOI":"10.1128\/JVI.00150-11","article-title":"Regulation of Antinucleoprotein IgG by Systemic Vaccination and Its Effect on Influenza Virus Clearance","volume":"85","author":"LaMere","year":"2011","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6363","DOI":"10.1016\/j.vaccine.2009.01.016","article-title":"Influenza virus CTL epitopes, remarkably conserved and remarkably variable","volume":"27","author":"Rimmelzwaan","year":"2009","journal-title":"Vaccine"},{"key":"ref_86","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_87","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1073\/pnas.82.6.1785","article-title":"Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes","volume":"82","author":"Yewdell","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/994\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:18:09Z","timestamp":1760123889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,18]]},"references-count":87,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["v15040994"],"URL":"https:\/\/doi.org\/10.3390\/v15040994","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,18]]}}}