title: Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems.
abstract: The development of an anti-influenza vaccine with the potential for cross-protection against seasonal drift variants as well as occasionally emerging reassortant viruses is essential. In this study, we successfully generated a novel anti-influenza vaccine system combining conserved matrix protein 2 (sM2) and stalk domain of hemagglutinin (HA2) fusion protein (sM2HA2) and poly-γ-glutamic acid (γ-PGA)-based vaccine adjuvant systems that can act as a mucoadhesive delivery vehicle of sM2HA2 as well as a robust strategy for the incorporation of hydrophobic immunostimulatory 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS21. Intranasal coadministration of sM2HA2 and the combination adjuvant γ-PGA/MPL/QS21 (CA-PMQ) was able to induce a high degree of protective mucosal, systemic, and cell-mediated immune responses. The sM2HA2/CA-PMQ immunization was able to prevent disease symptoms, confering complete protection against lethal infection with divergent influenza subtypes (H5N1, H1N1, H5N2, H7N3, and H9N2) that lasted for at least 6 mo. Therefore, our data suggest that mucosal administration of sM2HA2 in combination with CA-PMQ could be a potent strategy for a broad cross-protective influenza vaccine, and CA-PMQ as a mucosal adjuvant could be used for effective mucosal vaccines.
authors.affiliation: Department of Chemical Engineering, Sungkyunkwan University Advanced Institute of Nanotechnology, Suwon 440-746, South Korea;
authors.forename: Hyun Jong
authors.initials: HJ
authors.lastname: Noh
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea; Faculty of Veterinary Medicine, Chittagong Veterinary and Animal Sciences University, Chittagong 4202, Bangladesh;
authors.forename: Mohammed Y E
authors.initials: MY
authors.lastname: Chowdhury
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea;
authors.forename: Seonghun
authors.initials: S
authors.lastname: Cho
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea;
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Korea Basic Science Institute, Chungbuk 363-883, South Korea;
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea;
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea; and.
authors.forename: Haryoung
authors.initials: H
authors.lastname: Poo
authors.affiliation: Department of Advanced Fermentation Fusion Science and Technology, Kookmin University, Seoul 136-702, South Korea.
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, South Korea; jongsool@cnu.ac.kr yongtaik@skku.edu.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Chemical Engineering, Sungkyunkwan University Advanced Institute of Nanotechnology, Suwon 440-746, South Korea; jongsool@cnu.ac.kr yongtaik@skku.edu.
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D056738:Cross Protection / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007107:Immune System / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology / Q000502:physiology; D053125:Influenza A Virus, H5N2 Subtype / Q000276:immunology / Q000502:physiology; D057920:Influenza A Virus, H7N3 Subtype / Q000276:immunology / Q000502:physiology; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology / Q000502:physiology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology; D011108:Polymers / Q000737:chemistry*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011099:Polyglutamic Acid; D011108:Polymers; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C511775:poly(gamma-glutamic acid)