title: Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140.
abstract: The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss, J. Virol. 68:3015-3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHIV-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication.
authors.affiliation: Laboratory of Viral Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0455, USA. pearl@nih.gov
authors.forename: P L
authors.initials: PL
authors.lastname: Earl
authors.forename: W
authors.initials: W
authors.lastname: Sugiura
authors.forename: D C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: C C
authors.initials: CC
authors.lastname: Broder
authors.forename: S A
authors.initials: SA
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Wild
authors.forename: J
authors.initials: J
authors.lastname: Lifson
authors.forename: B
authors.initials: B
authors.lastname: Moss
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D003429:Cross Reactions; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008253:Macaca mulatta; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D011817:Rabbits; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology; D014611:Vaccination / Q000379:methods; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1