title: Evaluation of the antigenic relatedness and cross-protective immunity of the neuraminidase between human influenza A (H1N1) virus and highly pathogenic avian influenza A (H5N1) virus.
abstract: To determine the genetic and antigenic relatedness as well as the cross-protective immunity of human H1N1 and avian H5N1 influenza virus neuraminidase (NA), we immunized rabbits with either a baculovirus-expressed recombinant NA from A/Beijing/262/95 (BJ/262) H1N1 or A/Hong Kong/483/97 (HK/483) H5N1 virus. Cross-reactive antibody responses were evaluated by multiple serological assays and cross-protection against H5N1 virus challenge was evaluated in mice. In a neuraminidase inhibition (NI) test, the antisera exhibited substantial inhibition of NA activity of the homologous virus, but failed to inhibit the NA activity of heterologous virus. However, these antisera exhibited low levels of cross-reactivity measured by plaque size reduction, replication inhibition, single radial hemolysis, and ELISA assays. Passive immunization with HK/483 NA-specific antisera significantly reduced virus replication and disease, and afforded almost complete protection against lethal homologous virus challenge in mice. However, passive immunization with BJ/262 (H1N1) NA-specific antisera was ineffective at providing cross-protection against lethal H5N1 virus challenge and only slightly reduced weight loss. Substantial amino acid variation among the NA antigenic sites was observed between BJ/262 and HK/483 virus, which was consistent with the lack of cross-reactive NI activity by the antibody and limited cross-protective immunity in mice. These results show a strong correlation between the lack of cross-protective immunity and low structural similarities of NA from a human seasonal H1N1 virus and an avian H5N1 influenza virus.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Lu
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Sheu
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Jenna E
authors.initials: JE
authors.lastname: Achenbach
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Vic
authors.initials: V
authors.lastname: Veguilla
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Gubareva
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Garten
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Smith
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: James
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. Electronic address: TTumpey@cdc.gov.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection; D003429:Cross Reactions; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007116:Immunization, Passive; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology*; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011817:Rabbits; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: Anti-neuraminidase antibodies; Antigenic and genetic analyses; BALB/c mice; Cross-protective immunity; Influenza virus; Passive immunization