title: Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs.
abstract: Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract.
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
authors.forename: Varun
authors.initials: V
authors.lastname: Dwivedi
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
authors.forename: Cordelia
authors.initials: C
authors.lastname: Manickam
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
authors.forename: Santosh
authors.initials: S
authors.lastname: Dhakal
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
authors.forename: Basavaraj
authors.initials: B
authors.lastname: Binjawadagi
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States; College of Animal Science and Technology, Guangxi University, Nanning, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Ouyang
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States; Indian Council of Agricultural Research, National Institute of Veterinary Epidemiology and Disease Informatics, Bangalore, India.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Hiremath
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Khatri
authors.affiliation: Department of Chemistry, University of California Davis, One Shields Avenue, Davis, CA 95616, United States.
authors.forename: Jacquelyn Gervay
authors.initials: JG
authors.lastname: Hague
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States. Electronic address: gourapura.1@osu.edu.
authors.forename: Gourapura J
authors.initials: GJ
authors.lastname: Renukaradhya
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D055611:Natural Killer T-Cells / Q000737:chemistry / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000503:physiopathology / Q000662:veterinary*; D011897:Random Allocation; D013552:Swine; D013553:Swine Diseases / Q000276:immunology* / Q000503:physiopathology; D015164:Vaccines, Inactivated / Q000276:immunology; D019562:Viral Load; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D005699:Galactosylceramides; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; C493154:alpha-galactosylceramide
keywords: Adjuvant; Intranasal vaccine; Pigs; Swine influenza virus; iNKT cell; α-GalCer