title: A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.
abstract: BACKGROUND
  A key missing element in the development of a successful human immunodeficiency virus (HIV) vaccine is an immunogen that can generate broadly cross-neutralizing antibodies against primary isolates of the virus.
  
  
  METHODS
  This phase 1 clinical trial employed a DNA prime and subunit envelope protein boost in an attempt to generate cellular and humoral immune responses that might be desirable in a protective HIV vaccine. Priming was performed via intramuscular injection with gag and env DNA adsorbed to polylactide coglycolide microspheres, followed by boosting with a recombinant trimeric envelope (Env) glycoprotein delivered in MF59 adjuvant.
  
  
  RESULTS
  The DNA prime and protein boost were generally safe and well-tolerated. Env-specific CD4(+) cellular responses were generated that were predominantly detected after Env protein boosting. Neutralizing antibody responses against the homologous SF162 viral isolate were remarkably strong and were present in the majority of vaccine recipients, including a strong response against CD4-induced epitopes on gp120. Despite the promising potency of this vaccine approach, neutralization breadth against heterologous tier 2 strains of HIV-1 was minimal.
  
  
  CONCLUSIONS
  Potent neutralization against neutralization-sensitive strains of HIV is achievable in humans through a DNA prime, recombinant oligomeric Env protein boost regimen. Eliciting substantial breadth of neutralization remains an elusive goal.
  
  
  BACKGROUND
  NCT00073216.
authors: Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Georgia 30322, USA. paul.spearman@emory.edu
authors: Paul
authors: P
authors: Spearman
authors: Michelle A
authors: MA
authors: Lally
authors: Marnie
authors: M
authors: Elizaga
authors: David
authors: D
authors: Montefiori
authors: Georgia D
authors: GD
authors: Tomaras
authors: M Juliana
authors: MJ
authors: McElrath
authors: John
authors: J
authors: Hural
authors: Stephen C
authors: SC
authors: De Rosa
authors: Alicia
authors: A
authors: Sato
authors: Yunda
authors: Y
authors: Huang
authors: Sharon E
authors: SE
authors: Frey
authors: Paul
authors: P
authors: Sato
authors: John
authors: J
authors: Donnelly
authors: Susan
authors: S
authors: Barnett
authors: Lawrence J
authors: LJ
authors: Corey
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D000328:Adult; D057134:Antibodies, Neutralizing; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D004279:DNA, Viral; D018604:Epitope Mapping; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D004279:DNA, Viral; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1