title: Selection of HIV-specific immunogenic epitopes by screening random peptide libraries with HIV-1-positive sera.
abstract: Efforts to develop a protective HIV-1 vaccine have been hindered by difficulties in identifying epitopes capable of inducing broad neutralizing Ab responses. In fact, the high mutation rate occurring in HIV-1 envelope proteins and the complex structure of gp120 as an oligomer associated with gp41 result in a high degree of antigenic polymorphism. To overcome these obstacles, we screened random peptide libraries using sera from HIV-infected subjects to identify antigenic and immunogenic mimics of HIV-1 epitopes. After extensive counterscreening with HIV-negative sera, we isolated peptides specifically recognized by Abs from HIV-1-infected individuals. These peptides behaved as antigenic mimics of linear or conformational HIV-1 epitopes generated in vivo in infected subjects. Consistent with these findings, sera of simian HIV-infected monkeys also recognized the HIV-specific epitopes. The selected peptides were immunogenic in mice, where they elicited HIV-specific Abs that effectively neutralized HIV-1 isolates. These results demonstrate that pools of HIV-1 mimotopes can be selected from combinatorial peptide libraries by taking advantage of the HIV-specific Ab repertoire induced by the natural infection.
authors.affiliation: Laboratory of Immunoregulation, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. gscala@niaid.nih.gov
authors.forename: G
authors.initials: G
authors.lastname: Scala
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: J N
authors.initials: JN
authors.lastname: Telles
authors.forename: O J
authors.initials: OJ
authors.lastname: Cohen
authors.forename: M
authors.initials: M
authors.lastname: Vaccarezza
authors.forename: T
authors.initials: T
authors.lastname: Igarashi
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes; D015483:HIV Antibodies / Q000097:blood*; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D009500:Neutralization Tests; D009842:Oligopeptides / Q000276:immunology; D019151:Peptide Library
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D009842:Oligopeptides; D019151:Peptide Library