Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.
Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Jagadish
J
Hiremath
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Kyung-il
KI
Kang
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
Ming
M
Xia
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Mohamed
M
Elaish
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Basavaraj
B
Binjawadagi
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Kang
K
Ouyang
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Santosh
S
Dhakal
Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of America.
Jesus
J
Arcos
Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of America.
Jordi B
JB
Torrelles
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
X
X
Jiang
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Chang Won
CW
Lee
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Gourapura J
GJ
Renukaradhya
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D004285:Dogs; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009976:Orthomyxoviridae Infections / Q000276:immunology; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013552:Swine; D013553:Swine Diseases / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000737:chemistry / Q000276:immunology
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D010455:Peptides; D015164:Vaccines, Inactivated; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma