title: Heterosubtypic antibody response elicited with seasonal influenza vaccine correlates partial protection against highly pathogenic H5N1 virus.
abstract: BACKGROUND
  The spread of highly pathogenic avian influenza (HPAI) H5N1 virus in human remains a global health concern. Heterosubtypic antibody response between seasonal influenza vaccine and potential pandemic influenza virus has important implications for public health. Previous studies by Corti et al. and by Gioia et al. demonstrate that heterosubtypic neutralizing antibodies against the highly pathogenic H5N1 virus can be elicited with a seasonal influenza vaccine in humans. However, whether such response offers immune protection against highly pathogenic H5N1 virus remained to be determined.
  
  
  RESULTS
  In this study, using a sensitive influenza HA (hemagglutinin) and NA (neuraminidase) pseudotype-based neutralization (PN) assay we first confirmed that low levels of heterosubtypic neutralizing antibody response against H5N1 virus were indeed elicited with seasonal influenza vaccine in humans. We then immunized mice with the seasonal influenza vaccine and challenged them with lethal doses of highly pathogenic H5N1 virus. As controls, we immunized mice with homosubtypic H5N1 virus like particles (VLP) or PBS and challenged them with the same H5N1 virus. Here we show that low levels of heterosubtypic neutralizing antibody response were elicited with seasonal influenza vaccine in mice, which were significantly higher than those in PBS control. Among them 2 out of 27 whose immune sera exhibited similar levels of neutralizing antibody response as VLP controls actually survived from highly pathogenic H5N1 virus challenge.
  
  
  CONCLUSIONS
  Therefore, we conclude that low levels of heterosubtypic neutralizing antibody response are indeed elicited with seasonal influenza vaccine in humans and mice and at certain levels such response offers immune protection against severity of H5N1 virus infection.
authors.affiliation: Unit of Anti-Viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Ding
authors.forename: Cheguo
authors.initials: C
authors.lastname: Tsai
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.forename: Vincent
authors.initials: V
authors.lastname: Deubel
authors.forename: Paul
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D051379:Mice; D009439:Neuraminidase / Q000276:immunology; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D012621:Seasons; D017186:Titrimetry; D016896:Treatment Outcome; D053586:Virus Internalization
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007106:Immune Sera; D007252:Influenza Vaccines; D009439:Neuraminidase