title: Evaluation of envelope vaccines derived from the South African subtype C human immunodeficiency virus type 1 TV1 strain.
abstract: Human immunodeficiency virus type 1 (HIV-1) subtype C infections are on the rise in Sub-Saharan Africa and Asia. Therefore, there is a need to develop an HIV vaccine capable of eliciting broadly reactive immune responses against members of this subtype. We show here that modified HIV envelope (env) DNA vaccines derived from the South African subtype C TV1 strain are able to prime for humoral responses in rabbits and rhesus macaques. Priming rabbits with DNA plasmids encoding V2-deleted TV1 gp140 (gp140TV1DeltaV2), followed by boosting with oligomeric protein (o-gp140TV1DeltaV2) in MF59 adjuvant, elicited higher titers of env-binding and autologous neutralizing antibodies than priming with DNA vaccines encoding the full-length TV1 env (gp160) or the intact TV1 gp140. Immunization with V2-deleted subtype B SF162 env and V2-deleted TV1 env together using a multivalent vaccine approach induced high titers of oligomeric env-binding antibodies and autologous neutralizing antibodies against both the subtypes B and C vaccine strains, HIV-1 SF162 and TV1, respectively. Low-level neutralizing activity against the heterologous South African subtype C TV2 strain, as well as a small subset of viruses in a panel of 13 heterologous primary isolates, was observed in some rabbits immunized with the V2-deleted vaccines. Immunization of rhesus macaques with the V2-deleted TV1 DNA prime/protein boost also elicited high titers of env-binding antibodies and moderate titers of autologous TV1 neutralizing antibodies. The pilot-scale production of the various TV1 DNA vaccine constructs and env proteins described here should provide an initial platform upon which to improve the immunogenicity of these subtype C HIV envelope vaccines.
authors.affiliation: Chiron Corp., 4560 Horton St., 4.3, Emeryville, CA 94608. susan_barnett@chiron.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lian
authors.forename: Indresh
authors.initials: I
authors.lastname: Srivastava
authors.forename: V Rául
authors.initials: VR
authors.lastname: Gómez-Román
authors.forename: Jan
authors.initials: J
authors.lastname: Zur Megede
authors.forename: Yide
authors.initials: Y
authors.lastname: Sun
authors.forename: Elaine
authors.initials: E
authors.lastname: Kan
authors.forename: Susan
authors.initials: S
authors.lastname: Hilt
authors.forename: Susan
authors.initials: S
authors.lastname: Engelbrecht
authors.forename: Sunee
authors.initials: S
authors.lastname: Himathongkham
authors.forename: Paul A
authors.initials: PA
authors.lastname: Luciw
authors.forename: Gillis
authors.initials: G
authors.lastname: Otten
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Ulmer
authors.forename: John J
authors.initials: JJ
authors.lastname: Donnelly
authors.forename: Dietmar
authors.initials: D
authors.lastname: Rabussay
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Estrelita Janse
authors.initials: EJ
authors.lastname: van Rensburg
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D004353:Drug Evaluation, Preclinical; D017353:Gene Deletion; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D011817:Rabbits; D016415:Sequence Alignment; D013019:South Africa; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1