title: DNA prime and virus-like particle boost from a single H5N1 strain elicits broadly neutralizing antibody responses against head region of H5 hemagglutinin.
abstract: Since 1996, highly pathogenic avian influenza (HPAI) H5N1 virus has presented a persistent threat to public health. Its high degree of genetic diversity also poses enormous challenges in developing effective vaccines. To search for vaccine regimens that could elicit broadly neutralizing antibody responses against diverse HPAI H5N1 strains, in the present study we tested H5 hemagglutinin (HA) from an A/Thailand/1(KAN)-1/2004 strain in a heterologous prime-boost vaccination. We demonstrated that priming mice with DNA and boosting with virus-like particle induced antibody responses that cross-neutralize all reported clades and subclades of HPAI H5N1 viruses and protect mice from high lethal dose HPAI H5N1 challenge in both active and passive immunizations. Unexpectedly, cross-divergent H5 neutralizing antibodies are directed to the HA head and block both attachment and postattachment of virus entry. Thus, we conclude that as a promising pan-H5 vaccine candidate this prime-boost regimen could be further developed in ferrets and in humans.
authors.affiliation: Unit of Antiviral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guiqin
authors.initials: G
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.forename: Teng
authors.initials: T
authors.lastname: Zuo
authors.forename: Hongxing
authors.initials: H
authors.lastname: Hu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Song
authors.forename: Heng
authors.initials: H
authors.lastname: Ding
authors.forename: Cheguo
authors.initials: C
authors.lastname: Tsai
authors.forename: Ze
authors.initials: Z
authors.lastname: Chen
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Vincent
authors.initials: V
authors.lastname: Deubel
authors.forename: Paul
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics* / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D014611:Vaccination / Q000379:methods; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle; C109963:hemagglutinin, avian influenza A virus
keywords: HPAI H5N1; neutralizing antibody responses; vaccination