title: Induction of antibodies in guinea pigs and rhesus monkeys against the human immunodeficiency virus type 1 envelope: neutralization of nonpathogenic and pathogenic primary isolate simian/human immunodeficiency virus strains.
abstract: We have compared the abilities of human immunodeficiency virus type 1 (HIV-1) envelope V3 peptides and recombinant gp120 to induce antibodies that neutralize simian/human immunodeficiency viruses (SHIVs). SHIV-89.6 is a nonpathogenic SHIV that expresses the envelope protein of primary HIV-1 isolate 89.6. SHIV-89.6P, clone KB9, is a pathogenic SHIV variant derived from SHIV-89.6. Infection of rhesus monkeys with these SHIVs rarely induces anti-V3 region antibodies. To determine the availability of the gp120 V3 loop for neutralizing antibody binding on SHIV-89.6 and KB9 virions, we have constructed immunogenic C4-V3 peptides from these SHIVs and induced anti-V3 antibodies in guinea pigs and rhesus monkeys. We found that both SHIV-89.6 and KB9 C4-V3 peptides induced antibodies that neutralized SHIV-89.6 but that only SHIV-KB9 C4-V3 peptide induced antibodies that neutralized SHIV-KB9. Immunoprecipitation assays demonstrated that SHIV-KB9 C4-V3 peptide-induced antibodies had a greater ability to bind SHIV-KB9 envelope proteins than did antibodies raised against SHIV-89.6 C4-V3 peptide. We have used a series of mutant HIV-1 envelope constructs to map the gp120 determinants that affect neutralization by anti-V3 antibodies. The residue change at position 305 of arginine (in SHIV-89.6) to glutamic acid (in SHIV-KB9) played a central role in determining the ability of peptide-induced anti-V3 antiserum to neutralize primary isolate SHIVs. Moreover, residue changes in the SHIV-89.6 V1/V2 loops also played roles in regulating the availability of the V3 neutralizing epitope on SHIV-89.6 and -KB9. Thus, SHIV-89.6 and -KB9 V3 region peptides are capable of inducing neutralizing antibodies against these primary isolate SHIVs, although the pathogenic SHIV-KB9 is less easily neutralized than its nonpathogenic variant SHIV-89.6. In contrast to natural infection with SHIV-89.6, in which few animals make anti-V3 antibodies, C4-V3 peptides frequently induced anti-V3 antibodies that neutralized primary isolate SHIV strains.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: H X
authors.initials: HX
authors.lastname: Liao
authors.forename: B
authors.initials: B
authors.lastname: Etemad-Moghadam
authors.forename: D C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
authors.forename: R M
authors.initials: RM
authors.lastname: Scearce
authors.forename: R W
authors.initials: RW
authors.lastname: Doms
authors.forename: J R
authors.initials: JR
authors.lastname: Thomasch
authors.forename: S
authors.initials: S
authors.lastname: Robinson
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
authors.forename: B F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007106:Immune Sera; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010449:Peptide Mapping; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007106:Immune Sera; D011994:Recombinant Proteins