{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:12:06Z","timestamp":1783512726409,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIAID CEIRR","award":["75N93021C00014"],"award-info":[{"award-number":["75N93021C00014"]}]},{"name":"NIAID CEIRR","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"NIAID CEIRR","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]},{"name":"NIAID CEIRR","award":["HD092286"],"award-info":[{"award-number":["HD092286"]}]},{"name":"NIAID CEIRR","award":["AI158477"],"award-info":[{"award-number":["AI158477"]}]},{"name":"NIAID CEIRR","award":["2021-67015"],"award-info":[{"award-number":["2021-67015"]}]},{"name":"National Institutes of General Medical Sciences","award":["75N93021C00014"],"award-info":[{"award-number":["75N93021C00014"]}]},{"name":"National Institutes of General Medical Sciences","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"National Institutes of General Medical Sciences","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]},{"name":"National Institutes of General Medical Sciences","award":["HD092286"],"award-info":[{"award-number":["HD092286"]}]},{"name":"National Institutes of General Medical Sciences","award":["AI158477"],"award-info":[{"award-number":["AI158477"]}]},{"name":"National Institutes of General Medical Sciences","award":["2021-67015"],"award-info":[{"award-number":["2021-67015"]}]},{"name":"NIAID-supported Center of Excellence for Influenza Research and Response","award":["75N93021C00014"],"award-info":[{"award-number":["75N93021C00014"]}]},{"name":"NIAID-supported Center of Excellence for Influenza Research and Response","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"NIAID-supported Center of Excellence for Influenza Research and Response","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]},{"name":"NIAID-supported Center of Excellence for Influenza Research and Response","award":["HD092286"],"award-info":[{"award-number":["HD092286"]}]},{"name":"NIAID-supported Center of Excellence for Influenza Research and Response","award":["AI158477"],"award-info":[{"award-number":["AI158477"]}]},{"name":"NIAID-supported Center of Excellence for Influenza Research and Response","award":["2021-67015"],"award-info":[{"award-number":["2021-67015"]}]},{"name":"National Institutes of Health","award":["75N93021C00014"],"award-info":[{"award-number":["75N93021C00014"]}]},{"name":"National Institutes of Health","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"National Institutes of Health","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]},{"name":"National Institutes of Health","award":["HD092286"],"award-info":[{"award-number":["HD092286"]}]},{"name":"National Institutes of Health","award":["AI158477"],"award-info":[{"award-number":["AI158477"]}]},{"name":"National Institutes of Health","award":["2021-67015"],"award-info":[{"award-number":["2021-67015"]}]},{"name":"U.S. Department of Agriculture","award":["75N93021C00014"],"award-info":[{"award-number":["75N93021C00014"]}]},{"name":"U.S. Department of Agriculture","award":["P20GM130448"],"award-info":[{"award-number":["P20GM130448"]}]},{"name":"U.S. Department of Agriculture","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]},{"name":"U.S. Department of Agriculture","award":["HD092286"],"award-info":[{"award-number":["HD092286"]}]},{"name":"U.S. Department of Agriculture","award":["AI158477"],"award-info":[{"award-number":["AI158477"]}]},{"name":"U.S. Department of Agriculture","award":["2021-67015"],"award-info":[{"award-number":["2021-67015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Invariant natural killer T (iNKT) cells are glycolipid-reactive T cells with potent immunoregulatory properties. iNKT cells activated with the marine-sponge-derived glycolipid, \u03b1-galactosylceramide (\u03b1GC), provide a universal source of T-cell help that has shown considerable promise for a wide array of therapeutic applications. This includes harnessing iNKT-cell-mediated immune responses to adjuvant whole inactivated influenza virus (WIV) vaccines. An important concern with WIV vaccines is that under certain circumstances, they are capable of triggering vaccine-associated enhanced respiratory disease (VAERD). This immunopathological phenomenon can arise after immunization with an oil-in-water (OIW) adjuvanted WIV vaccine, followed by infection with a hemagglutinin and neuraminidase mismatched challenge virus. This elicits antibodies (Abs) that bind immunodominant epitopes in the HA2 region of the heterologous virus, which purportedly causes enhanced virus fusion activity to the host cell and increased infection. Here, we show that \u03b1GC can induce severe VAERD in pigs. However, instead of stimulating high concentrations of HA2 Abs, \u03b1GC elicits high concentrations of interferon (IFN)-\u03b3-secreting cells both in the lungs and systemically. Additionally, we found that VAERD mediated by iNKT cells results in distinct cytokine profiles and altered adaptation of the challenge virus following infection compared to an OIW adjuvant. Overall, these results provide a cautionary note about considering the formulation of WIV vaccines with iNKT-cell agonists as a potential strategy to modulate antigen-specific immunity.<\/jats:p>","DOI":"10.3390\/vaccines12091068","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T03:34:20Z","timestamp":1726716860000},"page":"1068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Adjuvant Use of the Invariant-Natural-Killer-T-Cell Agonist \u03b1-Galactosylceramide Leads to Vaccine-Associated Enhanced Respiratory Disease in Influenza-Vaccinated Pigs"],"prefix":"10.3390","volume":"12","author":[{"given":"Bianca L.","family":"Artiaga","sequence":"first","affiliation":[{"name":"Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Madden","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeyong","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8452-7288","authenticated-orcid":false,"given":"Chester","family":"McDowell","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassidy","family":"Keating","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1671-5572","authenticated-orcid":false,"given":"Velmurugan","family":"Balaraman","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darling Melany","family":"de Carvahlo Madrid","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Touchard","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Henningson","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Meade","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-776X","authenticated-orcid":false,"given":"Florian","family":"Krammer","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Morozov","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, 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infections","volume":"268","author":"Taylor","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/rmv.405","article-title":"Antibody-dependent enhancement of viral infection: Molecular mechanisms and in vivo implications","volume":"13","author":"Takada","year":"2003","journal-title":"Rev. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Smatti, M.K., Al Thani, A.A., and Yassine, H.M. (2018). Viral-Induced Enhanced Disease Illness. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02991"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1086\/651171","article-title":"Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus","volume":"201","author":"Kobinger","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.vetmic.2007.07.011","article-title":"Failure of protection and enhanced pneumonia with a US H1N2 swine influenza virus in pigs vaccinated with an inactivated classical swine H1N1 vaccine","volume":"126","author":"Vincent","year":"2008","journal-title":"Vet. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1177\/0300985812439724","article-title":"Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A\/H1N1 influenza virus","volume":"49","author":"Gauger","year":"2012","journal-title":"Vet. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1016\/j.vaccine.2011.01.082","article-title":"Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (\u03b4-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus","volume":"29","author":"Gauger","year":"2011","journal-title":"Vaccine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e0172521","DOI":"10.1128\/jvi.01725-21","article-title":"Vaccine-Associated Enhanced Respiratory Disease following Influenza Virus Infection in Ferrets Recapitulates the Model in Pigs","volume":"96","author":"Kimble","year":"2022","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1128\/jvi.62.1.20-26.1988","article-title":"Antibody-mediated growth of influenza A NWS virus in macrophagelike cell line P388D1","volume":"62","author":"Ochiai","year":"1988","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/jmv.1890300406","article-title":"Infection enhancement of influenza A H1 subtype viruses in macrophage-like P388D1 cells by cross-reactive antibodies","volume":"30","author":"Ochiai","year":"1990","journal-title":"J. Med. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nm.2262","article-title":"Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes","volume":"17","author":"Monsalvo","year":"2011","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Skowronski, D.M., De Serres, G., Crowcroft, N.S., Janjua, N.Z., Boulianne, N., Hottes, T.S., Rosella, L.C., Dickinson, J.A., Gilca, R., and Sethi, P. (2010). Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: Four observational studies from Canada. PLoS Med., 7.","DOI":"10.1371\/journal.pmed.1000258"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1086\/656586","article-title":"Seasonal influenza vaccine and increased risk of pandemic A\/H1N1-related illness: First detection of the association in British Columbia, Canada","volume":"51","author":"Janjua","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200ra114","DOI":"10.1126\/scitranslmed.3006366","article-title":"Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease","volume":"5","author":"Khurana","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1016\/j.vaccine.2018.08.072","article-title":"The type of adjuvant in whole inactivated influenza a virus vaccines impacts vaccine-associated enhanced respiratory disease","volume":"36","author":"Souza","year":"2018","journal-title":"Vaccine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1016\/j.vaccine.2014.07.059","article-title":"Influenza A virus hemagglutinin protein subunit vaccine elicits vaccine-associated enhanced respiratory disease in pigs","volume":"32","author":"Loving","year":"2014","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1089\/vim.2013.0018","article-title":"Vaccine-associated enhanced respiratory disease does not interfere with the adaptive immune response following challenge with pandemic A\/H1N1 2009","volume":"26","author":"Gauger","year":"2013","journal-title":"Viral Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1099\/jgv.0.000468","article-title":"Vaccine-associated enhanced respiratory disease is influenced by haemagglutinin and neuraminidase in whole inactivated influenza virus vaccines","volume":"97","author":"Chen","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/CVI.00563-15","article-title":"Age at Vaccination and Timing of Infection Do Not Alter Vaccine-Associated Enhanced Respiratory Disease in Influenza A Virus-Infected Pigs","volume":"23","author":"Souza","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41392-023-01557-7","article-title":"Vaccine adjuvants: Mechanisms and platforms","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Joyce, S., Okoye, G.D., and Driver, J.P. (2023). Die K\u00e4mpfe \u00fand schl\u00e1chten-the struggles and battles of innate-like effector T lymphocytes with microbes. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1117825"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6012","DOI":"10.4049\/jimmunol.166.10.6012","article-title":"Differential regulation of Th1 and Th2 functions of NKT cells by CD28 and CD40 costimulatory pathways","volume":"166","author":"Hayakawa","year":"2001","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00441-010-1023-3","article-title":"Invariant natural killer T cells: Bridging innate and adaptive immunity","volume":"343","author":"Parekh","year":"2011","journal-title":"Cell Tissue Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.immunol.25.022106.141711","article-title":"The biology of NKT cells","volume":"25","author":"Bendelac","year":"2007","journal-title":"Annu Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1002\/eji.200939594","article-title":"Alpha-GalCer ameliorates listeriosis by accelerating infiltration of Gr-1+ cells into the liver","volume":"40","author":"Emoto","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.4049\/jimmunol.169.3.1340","article-title":"The V alpha 14 NKT cell TCR exhibits high-affinity binding to a glycolipid\/CD1d complex","volume":"169","author":"Sidobre","year":"2002","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40265-016-0675-z","article-title":"Engaging Natural Killer T Cells as \u2019Universal Helpers\u2019 for Vaccination","volume":"77","author":"Speir","year":"2017","journal-title":"Drugs"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nri2451","article-title":"Harnessing invariant NKT cells in vaccination strategies","volume":"9","author":"Cerundolo","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"iqab013","DOI":"10.1093\/oxfimm\/iqab013","article-title":"Harnessing NKT cells for vaccination","volume":"2","author":"Burn","year":"2021","journal-title":"Oxf. Open Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fujii, S.-i., Yamasaki, S., Sato, Y., and Shimizu, K. (2018). Vaccine Designs Utilizing Invariant NKT-Licensed Antigen-Presenting Cells Provide NKT or T Cell Help for B Cell Responses. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01267"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8345","DOI":"10.1073\/pnas.0802968105","article-title":"B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo","volume":"105","author":"Barral","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/ni.2166","article-title":"Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses","volume":"13","author":"Chang","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Driver, J.P., de Carvalho Madrid, D.M., Gu, W., Artiaga, B.L., and Richt, J.A. (2020). Modulation of Immune Responses to Influenza A Virus Vaccines by Natural Killer T Cells. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.02172"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3201\/eid1603.091737","article-title":"Influenza A pandemic (H1N1) 2009 virus infection in domestic cat","volume":"16","author":"Sponseller","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_35","unstructured":"WHO (2002). WHO Manual on Animal Influenza Diagnosis and Surveillance, World Health Organization."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7535","DOI":"10.1128\/JVI.79.12.7535-7543.2005","article-title":"Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs","volume":"79","author":"Webby","year":"2005","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s44149-022-00051-x","article-title":"Evaluating \u03b1-galactosylceramide as an adjuvant for live attenuated influenza vaccines in pigs","volume":"2","author":"Artiaga","year":"2022","journal-title":"Anim. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method for estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetimm.2014.09.006","article-title":"Adjuvant effects of therapeutic glycolipids administered to a cohort of NKT cell-diverse pigs","volume":"162","author":"Artiaga","year":"2014","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Artiaga, B.L., Yang, G., Hackmann, T.J., Liu, Q., Richt, J.A., Salek-Ardakani, S., Castleman, W.L., Lednicky, J.A., and Driver, J.P. (2016). \u03b1-Galactosylceramide protects swine against influenza infection when administered as a vaccine adjuvant. Sci. Rep., 6.","DOI":"10.1038\/srep23593"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-1-61779-621-0_11","article-title":"Influenza A virus molecular virology techniques","volume":"865","author":"Zhou","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D339","DOI":"10.1093\/nar\/gky1006","article-title":"The Immune Epitope Database (IEDB): 2018 update","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/978-1-4939-0758-8_24","article-title":"Hemagglutinin inhibition assay with swine sera","volume":"1161","author":"Kitikoon","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sunwoo, S.Y., Schotsaert, M., Morozov, I., Davis, A.S., Li, Y., Lee, J., McDowell, C., Meade, P., Nachbagauer, R., and Garc\u00eda-Sastre, A. (2018). A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies. Vaccines, 6.","DOI":"10.3390\/vaccines6030064"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1177\/030098589503200606","article-title":"Comparison of the pathogenicity of two US porcine reproductive and respiratory syndrome virus isolates with that of the Lelystad virus","volume":"32","author":"Halbur","year":"1995","journal-title":"Vet. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1399-0039.1990.tb01772.x","article-title":"Characterization of a porcine CD1-specific mAb that distinguishes CD4\/CD8 double-positive thymic from peripheral T lymphocytes","volume":"35","author":"Pescovitz","year":"1990","journal-title":"Tissue Antigens"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1046\/j.1365-2567.1996.d01-705.x","article-title":"Phenotypic classification of porcine lymphocyte subpopulations in blood and lymphoid tissues","volume":"89","author":"Yang","year":"1996","journal-title":"Immunology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1046\/j.1365-2567.1996.494570.x","article-title":"Distribution of porcine CD4\/CD8 double-positive T lymphocytes in mucosa-associated lymphoid tissues","volume":"87","author":"Zuckermann","year":"1996","journal-title":"Immunology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Iyoda, T., Yamasaki, S., Ueda, S., Shimizu, K., and Fujii, S.I. (2023). Natural Killer T and Natural Killer Cell-Based Immunotherapy Strategies Targeting Cancer. Biomolecules, 13.","DOI":"10.3390\/biom13020348"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Nelson, A., Lukacs, J.D., and Johnston, B. (2021). The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead. Cancers, 13.","DOI":"10.3390\/cancers13205174"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/cei.12132","article-title":"In-vivo stimulation of macaque natural killer T cells with \u03b1-galactosylceramide","volume":"173","author":"Fernandez","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.3389\/fimmu.2019.01380","article-title":"Porcine Invariant Natural Killer T Cells: Functional Profiling and Dynamics in Steady State and Viral Infections","volume":"10","author":"Schwaiger","year":"2019","journal-title":"Front Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.vetimm.2012.06.023","article-title":"Identification of invariant natural killer T cells in porcine peripheral blood","volume":"149","author":"Thierry","year":"2012","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s10875-010-9476-4","article-title":"Functional invariant NKT cells in pig lungs regulate the airway hyperreactivity: A potential animal model","volume":"31","author":"Renukaradhya","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Madrid, D.M.C., Gu, W., Artiaga, B.L., Yang, G., Loeb, J., Hawkins, I.K., Castleman, W.L., Lednicky, J.A., Richt, J.A., and Driver, J.P. (2022). Comparison of oseltamivir and \u03b1-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.999507"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103843","DOI":"10.1016\/j.dci.2020.103843","article-title":"Unaltered influenza disease outcomes in swine prophylactically treated with \u03b1-galactosylceramide","volume":"114","author":"Gu","year":"2021","journal-title":"Dev. Comp. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Artiaga, B.L., Yang, G., Hutchinson, T.E., Loeb, J.C., Richt, J.A., Lednicky, J.A., Salek-Ardakani, S., and Driver, J.P. (2016). Rapid control of pandemic H1N1 influenza by targeting NKT-cells. Sci. Rep., 6.","DOI":"10.1038\/srep37999"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/imr.13201","article-title":"Tissue-resident memory T cells and lung immunopathology","volume":"316","author":"Cheon","year":"2023","journal-title":"Immunol. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.tim.2018.02.007","article-title":"Within-Host Evolution of Human Influenza Virus","volume":"26","author":"Xue","year":"2018","journal-title":"Trends Microbiol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/9\/1068\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:58:59Z","timestamp":1760111939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/9\/1068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,18]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["vaccines12091068"],"URL":"https:\/\/doi.org\/10.3390\/vaccines12091068","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,18]]}}}