title: Multiple-clade H5N1 influenza split vaccine elicits broad cross protection against lethal influenza virus challenge in mice by intranasal vaccination.
abstract: BACKGROUND
  The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model.
  
  
  RESULTS
  Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 µg HA per dose) included rg-A/Vietnam/1203/2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 µg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60% in single A/Anhui/1/2005 vaccine group.
  
  
  CONCLUSIONS
  Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination against unknown pandemic virus.
authors.affiliation: Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.
authors.forename: Penghui
authors.initials: P
authors.lastname: Yang
authors.forename: Yueqiang
authors.initials: Y
authors.lastname: Duan
authors.forename: Peirui
authors.initials: P
authors.lastname: Zhang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.forename: Chong
authors.initials: C
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Hongjing
authors.initials: H
authors.lastname: Gu
authors.forename: Zhongpeng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xiufan
authors.initials: X
authors.lastname: Liu
authors.forename: Shaogeng
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiliang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D056738:Cross Protection / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D013045:Species Specificity; D014611:Vaccination / Q000379:methods; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma