title: Superior neutralizing antibody response and protection in mice vaccinated with heterologous DNA prime and virus like particle boost against HPAI H5N1 virus.
abstract: BACKGROUND
  Although DNA plasmid and virus-like particle (VLP) vaccines have been individually tested against highly pathogenic avian influenza (HPAI) H5N1 viruses, the combination of both vaccines into a heterologous prime-boost strategy against HPAI H5N1 viruses has not been reported before.
  
  
  RESULTS
  We constructed DNA plasmid encoding H5HA (A/Shenzhen/406H/06, subclade 2.3.4) and generated VLP expressing the same H5HA and N1NA. We then compared neutralizing antibody responses and immune protection elicited with heterologous DNA-VLP, homologous DNA-DNA and VLP-VLP prime-boost strategies against HPAI H5N1 viruses in mice. We demonstrate that DNA-VLP elicits the highest neutralizing antibody titers among the three prime-boost strategies, whereas DNA-DNA elicits higher neutralizing antibody titers than VLP-VLP. We show that although all three prime-boost strategies protect mice from death caused by 10 MLD(50) of homologous and heterologous H5N1 challenge, only DNA-VLP and DNA-DNA protect mice from infection as manifested by no weight loss and no lung pathology. In addition, we show that although DNA-VLP and DNA-DNA protect mice from death caused by 1,000 MLD(50) of homologous H5N1 challenge, only DNA-VLP protects mice from infection. Moreover, we show that after 1,000 MLD(50) of heterologous H5N1 challenge, while all mice in PBS, VLP-VLP and DNA-DNA died, 3 of 6 mice in DNA-VLP actually survived. Finally, we show that DNA-VLP completely protects mice from infection after 1,000 MLD(50) of homologous H5N1 challenge even when the challenge was administrated at 60 days post the boost.
  
  
  CONCLUSIONS
  These results provide strong support for clinical evaluation of heterologous DNA-VLP prime-boost strategy as a public health intervention against a possible H5N1 pandemic.
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: Ramona Alikiiteaga
authors.initials: RA
authors.lastname: Gutiérrez
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: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000628:therapy; D016896:Treatment Outcome; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D058425:Vaccines, Virus-Like Particle