title: Broad HIV-1 neutralizing antibody response induced by heterologous gp140/gp145 DNA prime-vaccinia boost immunization.
abstract: OBJECTIVE
  To develop an effective HIV vaccine strategy that can induce cross-reactive neutralizing antibody.
  
  
  METHODS
  Codon-optimized gp140 and gp145 env genes derived from HIV-1(cn54), a CRF07 B'/C recombinant strain, were constructed as DNA and recombinant Tiantan vaccinia (rTV) vaccines. The effect of heterologous immunization with gp140 and gp145 was tested in mice and guinea pigs. T cell responses were detected using the IFN-γ ELISPOT assay. A panel of primary isolates of clade B' and B'/C HIV-1 and TZM-bl cells was used to determine the neutralizing activity of immunized sera.
  
  
  RESULTS
  The neutralizing antibodies (NAbs) induced by the heterologous immunogen immunization neutralized all HIV-1 B' and B'/C primary isolates in the guinea pig model. Gp145 and gp140 heterologous prime-boost induced the best neutralizing antibody response with a broad neutralizing spectrum and the highest titer of 1:270 at 6 weeks after the last inoculation. However, the T cell response to HIV-1 peptides was significantly weaker than the gp145+gp145 homologous prime-boost.
  
  
  CONCLUSIONS
  This heterologous prime-boost immunization strategy could be used to design immunogen-generating broad neutralizing antibodies against genetic variance pathogens.
authors.affiliation: State Key Laboratory for Infectious Diseases Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China.
authors.forename: Lianxing
authors.initials: L
authors.lastname: Liu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hao
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Luo
authors.forename: Yang
authors.initials: Y
authors.lastname: Huang
authors.forename: Xintao
authors.initials: X
authors.lastname: Hu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005822:Genetic Vectors; D006168:Guinea Pigs; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; D007371:Interferon-gamma