title: Recombinant trimeric HA protein immunogenicity of H5N1 avian influenza viruses and their combined use with inactivated or adenovirus vaccines.
abstract: BACKGROUND
  The highly pathogenic avian influenza (HPAI) H5N1 virus continues to cause disease in poultry and humans. The hemagglutinin (HA) envelope protein is the primary target for subunit vaccine development.
  
  
  RESULTS
  We used baculovirus-insect cell expression to obtain trimeric recombinant HA (rHA) proteins from two HPAI H5N1 viruses. We investigated trimeric rHA protein immunogenicity in mice via immunizations, and found that the highest levels of neutralizing antibodies resulted from coupling with a PELC/CpG adjuvant. We also found that the combined use of trimeric rHA proteins with (a) an inactivated H5N1 vaccine virus, or (b) a recombinant adenovirus encoding full-length HA sequences for prime-boost immunization, further improved antibody responses against homologous and heterologous H5N1 virus strains. Data from cross-clade prime-boost immunization regimens indicate that sequential immunization with different clade HA antigens increased antibody responses in terms of total IgG level and neutralizing antibody titers.
  
  
  CONCLUSIONS
  Our findings suggest that the use of trimeric rHA in prime-boost vaccine regimens represents an alternative strategy for recombinant H5N1 vaccine development.
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Lin
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Huang
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Tsou
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.forename: Suh-Chin
authors.initials: SC
authors.lastname: Wu
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines