title: Analysis of HIV-1 subtype B third variable region peptide motifs for induction of neutralizing antibodies against HIV-1 primary isolates.
abstract: The HIV-1 gp120 V3 loop is a potent inducer of neutralizing antibodies for T cell line adapted-HIV-1, but less so for primary isolates. We hypothesized that peptides representative of the diversity of natural HIV-1 V3 loop variants might capture elements of conserved higher order structures and so stimulate broadly reactive neutralizing antibodies. We designed a panel of 29 subtype B V3 sequences postulated to reflect the range of V3 diversity. These peptides were used to immunize guinea pigs. The most effective peptide (62.19) clustered around the subtype B consensus sequence and induced antibodies that reproducibly neutralized 31% of the subtype B HIV-1 primary isolates evaluated, but exhibited limited cross-neutralization of non-subtype B HIV-1 strains. Taken together, these data demonstrated that the limited neutralization profile of antibodies induced by optimal subtype B V3 motifs likely represents the maximum breadth of neutralization of subtype B HIV-1 primary isolates attainable by anti-V3 peptide antibodies.
authors.affiliation: Department of Medicine and Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. hayne002@mc.duke.edu
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Benjiang
authors.initials: B
authors.lastname: Ma
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Christos J
authors.initials: CJ
authors.lastname: Petropoulos
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.forename: Cathrine
authors.initials: C
authors.lastname: Denton
authors.forename: Shi-Mao
authors.initials: SM
authors.lastname: Xia
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D016384:Consensus Sequence; D003429:Cross Reactions; D006168:Guinea Pigs; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
chemical_list: D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments