title: Polyanhydride nanovaccine against swine influenza virus in pigs.
abstract: We have recently demonstrated the effectiveness of an influenza A virus (IAV) subunit vaccine based on biodegradable polyanhydride nanoparticles delivery in mice. In the present study, we evaluated the efficacy of ∼200nm polyanhydride nanoparticles encapsulating inactivated swine influenza A virus (SwIAV) as a vaccine to induce protective immunity against a heterologous IAV challenge in pigs. Nursery pigs were vaccinated intranasally twice with inactivated SwIAV H1N2 (KAg) or polyanhydride nanoparticle-encapsulated KAg (KAg nanovaccine), and efficacy was evaluated against a heterologous zoonotic virulent SwIAV H1N1 challenge. Pigs were monitored for fever daily. Local and systemic antibody responses, antigen-specific proliferation of peripheral blood mononuclear cells, gross and microscopic lung lesions, and virus load in the respiratory tract were compared among the groups of animals. Our pre-challenge results indicated that KAg nanovaccine induced virus-specific lymphocyte proliferation and increased the frequency of CD4+CD8αα+T helper and CD8+cytotoxic T cells in peripheral blood mononuclear cells. KAg nanovaccine-immunized pigs were protected from fever following SwIAV challenge. In addition, pigs immunized with the KAg nanovaccine presented with lower viral antigens in lung sections and had 6 to 8-fold reduction in nasal shedding of SwIAV four days post-challenge compared to control animals. Immunologically, increased IFN-γ secreting T lymphocyte populations against both the vaccine and challenge viruses were detected in KAg nanovaccine-immunized pigs compared to the animals immunized with KAg alone. However, in the KAg nanovaccine-immunized pigs, hemagglutination inhibition, IgG and IgA antibody responses, and virus neutralization titers were comparable to that in the animals immunized with KAg alone. Overall, our data indicated that intranasal delivery of polyanhydride-based SwIAV nanovaccine augmented antigen-specific cellular immune response in pigs, with promise to induce cross-protective immunity.
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: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goodman
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: 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: 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: 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 Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
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
authors.initials: C
authors.lastname: Won Lee
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. Electronic address: gourapura.1@osu.edu.
authors.forename: Gourapura J
authors.initials: GJ
authors.lastname: Renukaradhya
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000187:drug effects; D006385:Hemagglutination Inhibition Tests; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000276:immunology; D057221:Influenza A Virus, H1N2 Subtype / Q000187:drug effects / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D049388:Polyanhydrides / Q000737:chemistry / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D015164:Vaccines, Inactivated; D019562:Viral Load / Q000187:drug effects
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D049388:Polyanhydrides; D015164:Vaccines, Inactivated; D007371:Interferon-gamma
keywords: Immunity; Intranasal; Pigs; Polyanhydride nanoparticles; Swine influenza virus