title: Intranasal vaccination of recombinant H5N1 HA1 proteins fused with foldon and Fc induces strong mucosal immune responses with neutralizing activity: Implication for developing novel mucosal influenza vaccines.
abstract: The highly pathogenic avian influenza (HPAI) H5N1 virus remains a threat to public health because of its continued spread in poultry in some countries and its ability to infect humans with high mortality rate, calling for the development of effective and safe vaccines against H5N1 infection. Here, we constructed 4 candidate vaccines by fusing H5N1 hemagglutinin 1 (HA1) with foldon (HA1-Fd), human IgG Fc (HA1-Fc), foldon and Fc (HA1-FdFc) or His-tag (HA1-His). We then compared their ability to induce mucosal immune responses and neutralizing antibodies in the presence or absence of Poly(I:C) and CpG adjuvants via the intranasal route. Without an adjuvant, HA1-FdFc could elicit appreciable humoral immune responses and local mucosal IgA antibodies in immunized mice, while other vaccine candidates only induced background immune responses. In the presence of Poly(I:C) and CpG, both HA1-Fd and HA1-Fc elicited much higher levels of serum IgG and local mucosal IgA antibodies than HA1-His. Poly(I:C) and CpG could also augment the neutralizing antibody responses induced by these 4 vaccine candidates in the order of HA1-FdFc > HA1-Fc > HA1-Fd > HA1-His. These results suggest that both Fd and Fc potentiate the immunogenicity of the recombinant HA1 protein and that Poly(I:C) and CpG serve as efficient mucosal adjuvants in promoting efficacy of these vaccine candidates to induce strong systemic and local antibody responses and potent neutralizing antibodies, providing a useful strategy to develop effective and safe mucosal H5N1 vaccines.
authors.affiliation: a Lindsley F. Kimball Research Institute; New York Blood Center ; New York , NY USA.|b Key Laboratory of Medical Molecular Virology of Ministries of Education and Health; Shanghai Medical College and Institute of Medical Microbiology; Fudan University ; Shanghai , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: a Lindsley F. Kimball Research Institute; New York Blood Center ; New York , NY USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: c State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology ; Beijing , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: a Lindsley F. Kimball Research Institute; New York Blood Center ; New York , NY USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Lindsley F. Kimball Research Institute; New York Blood Center ; New York , NY USA.|d Key Lab of New Drug Screening of Guangdong Province; School of Pharmaceutical Sciences; Southern Medical University ; Guangzhou , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: c State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology ; Beijing , China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhao
authors.affiliation: c State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology ; Beijing , China.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: a Lindsley F. Kimball Research Institute; New York Blood Center ; New York , NY USA.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: a Lindsley F. Kimball Research Institute; New York Blood Center ; New York , NY USA.|b Key Laboratory of Medical Molecular Virology of Ministries of Education and Health; Shanghai Medical College and Institute of Medical Microbiology; Fudan University ; Shanghai , China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D011070:Poly I-C
keywords: H5N1; HA1; Influenza virus; intranasal immunization; mucosal adjuvants; protein