title: Monovalent H5 vaccine based on epitope-chimeric HA provides broad cross-clade protection against variant H5N1 viruses in mice.
abstract: H5N1 HPAI virus continues to be a severe threat for public health, as well as for the poultry industry, due to its high mortality and antigenic drift rate. There is no monovalent vaccine available which provides broad protection against those major circulating strains. In the present study, a monovalent H5 vaccine strain was developed with antigenic sequence analysis and epitope mutations. H5 from Indonesia strain (A/Indonesia/CDC669/2006) was used as backbone sequence. Three amino acids were mutated to express immunogenic epitopes from other circulating H5N1s in the backbone. RG influenza virus expressing the epitope-chimeric H5 can react in HI with multiple H5 monoclonal antibodies which fail to neutralize wild type CDC669. High titers in HI and virus neutralization against different clades H5N1s (clade 1, 2, 4 and 7) were detected using sera from mice immunized with the epitope-chimeric H5N1. The monovalent vaccine with RG-epitope-chimeric H5N1 protected mice from lethal challenge with H5N1s of different clades, including clade 1.0, 2.1, 2.2 and 2.3. This study indicates that the broad immune response elicited by this single H5N1 virus allows it to be a promising candidate for a monovalent H5 universal vaccine.
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, Singapore, Singapore.
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, Singapore, Singapore.
authors.forename: Mookkan
authors.initials: M
authors.lastname: Prabakaran
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, Singapore, Singapore.
authors.forename: Subaschandrabose
authors.initials: S
authors.lastname: Rajesh Kumar
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, Singapore, Singapore.
authors.forename: Yunrui
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, Singapore, Singapore; Department of Microbiology Faculty of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: kwang@tll.org.sg.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kwang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D056738:Cross Protection; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
keywords: Cross clade; H5N1 AIV; Influenza vaccine; Monovalent