title: Mucosal immunization with recombinant influenza hemagglutinin protein and poly gamma-glutamate/chitosan nanoparticles induces protection against highly pathogenic influenza A virus.
abstract: Intranasal administration of recombinant influenza hemagglutinin (rHA) antigen or inactivated virus with nanoparticles (NPs) composed of poly-γ-glutamic acid (γ-PGA) and chitosan which are safe, natural materials, and able to target the mucosal membrane as a mucosal adjuvant, could induce a high degree of protective mucosal immunity in the respiratory tract. Intranasal immunization with mixture of rHA antigen or inactivated virus and γ-PGA/chitosan nanoparticles (PC NPs) induced not only a high anti-HA immunoglobulin A (IgA) response in lung and IgG response in serum, including anti-HA neutralizing antibodies, but also an influenza virus-specific cell-mediated immune response. Also, PC NPs could function as a potential mucosal adjuvant when it was compared with the well-known mucosal adjuvant, cholera toxin (CT). Intranasal administration of rHA antigen or inactivated virus with PC NPs protected mice against challenge with a lethal dose of the highly pathogenic influenza A H5N1 virus. These results suggested that application of PC NPs with a subunit antigen of influenza produced by prokaryotic expression system provides several solutions to the current problems of the influenza vaccines using inactivated influenza virus. Moreover, our finding about a sufficient function of PC NPs to elevate vaccine efficacy led us to consider that it can be useful in clinical applications as a potent mucosal adjuvant with safety.
authors: College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors: Ho-Jin
authors: HJ
authors: Moon
authors: Jong-Soo
authors: JS
authors: Lee
authors: Melbourne R
authors: MR
authors: Talactac
authors: Mohammed Y E
authors: MY
authors: Chowdhury
authors: Jae-Hoon
authors: JH
authors: Kim
authors: Min-Eun
authors: ME
authors: Park
authors: Young-Ki
authors: YK
authors: Choi
authors: Moon-Hee
authors: MH
authors: Sung
authors: Chul-Joong
authors: CJ
authors: Kim
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D048271:Chitosan / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007114:Immunization / Q000592:standards*; D007132:Immunoglobulin Isotypes; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007132:Immunoglobulin Isotypes; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D048271:Chitosan