title: Immunogenicity of HIV-1 Env and Gag in baboons using a DNA prime/protein boost regimen.
abstract: OBJECTIVE
  To evaluate the immunogenicity of sequence-modified HIV env and gag in baboons using DNA prime and protein boost strategy.
  
  
  METHODS
  Synthetic sequence-modified HIV gene cassettes were constructed that expressed three different forms of Env proteins, gp140, gp140mut and gp140TM, plus or minus a mutation in the protease-cleavage site. These plasmids were used to immunize baboons (Papio cynocephalus). A group of baboons was also immunized with both env and gag DNA followed by p55Gag virus-like particles (VLP) boost.
  
  
  RESULTS
  Modest antibody responses and low or no lymphoproliferative responses were observed following multiple DNA immunizations. In contrast, strong antibodies and substantial antigen-specific lymphoproliferative responses were seen following booster immunizations with oligomeric Env protein (o-gp140US4) in MF59. Neutralizing antibody responses were scored against T cell line adapted HIV-1 strains after the protein boosters, but neutralizing responses were low or absent against homologous and heterologous primary isolate strains. In the group receiving both gag and env vaccines, modest antigen-specific antibody and lymphoproliferative responses were scored after the DNA immunizations; these responses were enhanced several-fold upon boosting with the VLP preparations. The addition of Gag antigen did not interfere with Env-specific antibody responses, but there was a negative effect on the levels of Env-specific lymphoproliferation.
  
  
  CONCLUSIONS
  These results highlight the importance of improving the potency of HIV DNA vaccines by enhanced DNA delivery and prime-boost vaccine technologies to generate more robust immune responses in larger animal models. In addition, care must be taken when immunizations with Env and Gag antigens are performed together.
authors.affiliation: Chiron Corp., Emeryville, California 94608, USA.
authors.forename: Louisa
authors.initials: L
authors.lastname: Leung
authors.forename: Indresh K
authors.initials: IK
authors.lastname: Srivastava
authors.forename: Elaine
authors.initials: E
authors.lastname: Kan
authors.forename: Harold
authors.initials: H
authors.lastname: Legg
authors.forename: Yide
authors.initials: Y
authors.lastname: Sun
authors.forename: Catherine
authors.initials: C
authors.lastname: Greer
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Jan
authors.initials: J
authors.lastname: zur Megede
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000915:Antibody Affinity; D002455:Cell Division / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007117:Immunization, Secondary / Q000379:methods; D016254:Mutagenesis, Insertional; D010215:Papio; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1