title: Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs.
abstract: Swine influenza virus (SwIV) is one of the important zoonotic pathogens. Current flu vaccines have failed to provide cross-protection against evolving viruses in the field. Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable FDA approved polymer and widely used in drug and vaccine delivery. In this study, inactivated SwIV H1N2 antigens (KAg) encapsulated in PLGA nanoparticles (PLGA-KAg) were prepared, which were spherical in shape with 200 to 300nm diameter, and induced maturation of antigen presenting cells in vitro. Pigs vaccinated twice with PLGA-KAg via intranasal route showed increased antigen specific lymphocyte proliferation and enhanced the frequency of T-helper/memory and cytotoxic T cells (CTLs) in peripheral blood mononuclear cells (PBMCs). In PLGA-KAg vaccinated and heterologous SwIV H1N1 challenged pigs, clinical flu symptoms were absent, while the control pigs had fever for four days. Grossly and microscopically, reduced lung pathology and viral antigenic mass in the lung sections with clearance of infectious challenge virus in most of the PLGA-KAg vaccinated pig lung airways were observed. Immunologically, PLGA-KAg vaccine irrespective of not significantly boosting the mucosal antibody response, it augmented the frequency of IFN-γ secreting total T cells, T-helper and CTLs against both H1N2 and H1N1 SwIV. In summary, inactivated influenza virus delivered through PLGA-NPs reduced the clinical disease and induced cross-protective cell-mediated immune response in a pig model. Our data confirmed the utility of a pig model for intranasal particulate flu vaccine delivery platform to control flu in humans.
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Dhakal
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Hiremath
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Bondra
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yashavanth S
authors.initials: YS
authors.lastname: Lakshmanappa
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Duan-Liang
authors.initials: DL
authors.lastname: Shyu
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Ouyang
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Kyung-Il
authors.initials: KI
authors.lastname: Kang
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Basavaraj
authors.initials: B
authors.lastname: Binjawadagi
authors.affiliation: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goodman
authors.affiliation: The Research Institute for Biological Safety Problems (RIBSP), Zhambylskaya Oblast, Gvardeiskiy 080409, Kazakhstan.
authors.forename: Kairat
authors.initials: K
authors.lastname: Tabynov
authors.affiliation: The Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, Columbus, OH, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Krakowka
authors.affiliation: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA. Electronic address: gourapura.1@osu.edu.
authors.forename: Gourapura J
authors.initials: GJ
authors.lastname: Renukaradhya
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D002478:Cells, Cultured; D004285:Dogs; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry*; D061985:Madin Darby Canine Kidney Cells; D053758:Nanoparticles / Q000737:chemistry*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013552:Swine; D015164:Vaccines, Inactivated / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000956:Antigens, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Immune response; Intranasal vaccination; PLGA nanoparticles; Pigs; Swine influenza virus; T cells