title: Increased T cell breadth and antibody response elicited in prime-boost regimen by viral vector encoded homologous SIV Gag/Env in outbred CD1 mice.
abstract: A major obstacle for the development of HIV vaccines is the virus' worldwide sequence diversity. Nevertheless, the presence of T cell epitopes within conserved regions of the virus' structural Gag protein and conserved structures in the envelope (env) sequence raises the possibility that cross-reactive responses may be induced by vaccination. In this study, the aim was to investigate the importance of antigenic match on immunodominance and breadth of obtainable T cell responses.
  
  
  
  Outbred CD1 mice were immunized with either heterologous (SIVmac239 and HIV-1 clade B consensus) or homologous (SIVmac239) gag sequences using adenovirus (Ad5) and MVA vectors. Env (SIVmac239) was co-encoded in the vectors to study the induction of antibodies, which is a primary target of current HIV vaccine designs. All three vaccines were designed as virus-encoded virus-like particle vaccines. Antibody responses were analysed by ELISA, avidity ELISA, and neutralization assay. T cell responses were determined by intracellular cytokine staining of splenocytes.
  
  
  
  The homologous Env/Gag prime-boost regimen induced higher Env binding antibodies, and induced stronger and broader Gag specific CD8+ T cell responses than the homologous Env/heterologous Gag prime-boost regimen. Homologous Env/heterologous Gag immunization resulted in selective boosting of Env specific CD8+ T cell responses and consequently a paradoxical decreased recognition of variant sequences including conserved elements of p24 Gag.
  
  
  
  These results contrast with related studies using Env or Gag as the sole antigen and suggest that prime-boost immunizations based on homologous SIVmac239 Gag inserts is an efficient component of genetic VLP vaccines-both for induction of potent antibody responses and cross-reactive CD8+ T cell responses.
authors.affiliation: Department of Immunology and Microbiology, Center for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark. annema@sund.ku.dk.
authors.forename: Anne-Marie Carola
authors.initials: AC
authors.lastname: Andersson
authors.affiliation: Department of Immunology and Microbiology, Center for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark. pholst@sund.ku.dk.
authors.forename: Peter Johannes
authors.initials: PJ
authors.lastname: Holst
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D021461:Animals, Outbred Strains; D000914:Antibodies, Viral; D000917:Antibody Formation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D005822:Genetic Vectors / Q000378:metabolism*; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D007371:Interferon-gamma
keywords: Adenoviral vectors; Human immunodeficiency virus; Vaccine; Virus-like particles