title: Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity.
abstract: H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H5₃) was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H5₃ antigen was a robust immunogen. Immunizing mice with H5₃ encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4(+) T cell recall responses in mice. Finally, the H5₃-based polyanhydride nanovaccine induced protective immunity against a low-pathogenic H5N1 viral challenge. Informatics analyses indicated that mice receiving the nanovaccine formulations and subsequently challenged with virus were similar to naïve mice that were not challenged. The current studies provide a basis to further exploit the advantages of polyanhydride nanovaccines in pandemic scenarios.
authors.affiliation: Chemical and Biological Engineering, Iowa State University, Ames, IA, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ross
authors.affiliation: Animal Science, Iowa State University, Ames, IA, USA.
authors.forename: Hyelee
authors.initials: H
authors.lastname: Loyd
authors.affiliation: Animal Science, Iowa State University, Ames, IA, USA.
authors.forename: Wuwei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Huntimer
authors.affiliation: Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Shaheen
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Sambol
authors.affiliation: Materials Science and Engineering, Iowa State University, Ames, IA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Broderick
authors.affiliation: Animal Science, Iowa State University, Ames, IA, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Flickinger
authors.affiliation: Materials Science and Engineering, Iowa State University, Ames, IA, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Rajan
authors.affiliation: Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bronich
authors.affiliation: Chemical and Biological Engineering, Iowa State University, Ames, IA, USA.
authors.forename: Surya
authors.initials: S
authors.lastname: Mallapragada
authors.affiliation: Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
authors.affiliation: Animal Science, Iowa State University, Ames, IA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Carpenter
authors.affiliation: Chemical and Biological Engineering, Iowa State University, Ames, IA, USA.
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D049388:Polyanhydrides / Q000737:chemistry*; D025341:Principal Component Analysis; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D049388:Polyanhydrides; D014614:Vaccines, Synthetic; C109963:hemagglutinin, avian influenza A virus
keywords: nanoparticle; neutralizing antibody; polymer; subunit; vaccine