title: A recombinant vaccine of H5N1 HA1 fused with foldon and human IgG Fc induced complete cross-clade protection against divergent H5N1 viruses.
abstract: Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus.
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.forename: Virtual Ho-Chuen
authors.initials: VH
authors.lastname: Leung
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Wu
authors.initials: W
authors.lastname: He
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Chris C S
authors.initials: CC
authors.lastname: Chan
authors.forename: Vincent Kwok-Man
authors.initials: VK
authors.lastname: Poon
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhao
authors.forename: Shihui
authors.initials: S
authors.lastname: Sun
authors.forename: Lifeng
authors.initials: L
authors.lastname: Cai
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D056738:Cross Protection; D005818:Genetic Engineering; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007114:Immunization; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry* / Q000276:immunology; D007252:Influenza Vaccines; D051379:Mice; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007141:Immunoglobulin Fc Fragments; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic