title: Mucosal vaccination of conserved sM2, HA2 and cholera toxin subunit A1 (CTA1) fusion protein with poly gamma-glutamate/chitosan nanoparticles (PC NPs) induces protection against divergent influenza subtypes.
abstract: To develop a safe and effective mucosal vaccine that broad cross protection against seasonal or emerging influenza A viruses, we generated a mucosal influenza vaccine system combining the highly conserved matrix protein-2 (sM2), fusion peptide of hemagglutinin (HA2), the well-known mucosal adjuvant cholera toxin subunit A1 (CTA1) and poly-γ-glutamic acid (γ-PGA)-chitosan nanoparticles (PC NPs), which are safe, natural materials that are able to target the mucosal membrane as a mucosal adjuvant. The mucosal administration of sM2HA2CTA1/PC NPs could induce a high degree of systemic immunity (IgG and IgA) at the site of inoculation as well as at remote locations and also significantly increase the levels of sM2- or HA2-specific cell-mediated immune response. In challenge tests in BALB/c mice with 10 MLD50of A/EM/Korea/W149/06(H5N1), A/Puerto Rico/8/34(H1N1), A/Aquatic bird/Korea/W81/2005(H5N2), A/Aquatic bird/Korea/W44/2005 (H7N3) or A/Chicken/Korea/116/2004(H9N2) viruses, the recombinant sM2HA2CTA1/PC NPs provided cross protection against divergent lethal influenza subtypes and also the protection was maintained up to six months after vaccination. Thus, sM2HA2CTA1/PC NPs could be a promising strategy for a universal influenza vaccine.
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea; Faculty of Veterinary Medicine, Chittagong Veterinary and Animal Sciences University, Chittagong, Bangladesh.
authors.forename: Mohammed Y E
authors.initials: MYE
authors.lastname: Chowdhury
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea; Faculty of Veterinary & Animal Science, Sylhet Agricultural University, Sylhet -3100, Bangladesh.
authors.forename: Md Bashir
authors.initials: MB
authors.lastname: Uddin
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: C Y
authors.initials: CY
authors.lastname: Hewawaduge
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea; Department of Biochemistry and Biotechnology, University of Science and Technology Chittagong, Bangladesh.
authors.forename: Zannatul
authors.initials: Z
authors.lastname: Ferdowshi
authors.affiliation: BioLeaders Corporation, Daejeon, Republic of Korea.
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea. Electronic address: cjkim@cnu.ac.kr.
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea. Electronic address: jongsool@cnu.ac.kr.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D048271:Chitosan / Q000276:immunology; D002772:Cholera Toxin / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection / Q000276:immunology; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000276:immunology; D011993:Recombinant Fusion Proteins; D014611:Vaccination / Q000662:veterinary; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D006388:Hemagglutinins; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D002772:Cholera Toxin; D048271:Chitosan
keywords: Chitosan nanoparticles (PC NPs); Cholera toxin subunit A1 (CTA1); Hemagglutinin fusion peptide (HA2); Influenza vaccine; Matrix protein-2 (sM2); Mucosal immunity; Poly-γ-glutamic acid (γ-PGA)