Selection of HIV-specific immunogenic epitopes by screening random peptide libraries with HIV-1-positive sera.
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.
Scala
G
G
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
Chen
X
X
Liu
W
W
Telles
J N
JN
Cohen
O J
OJ
Vaccarezza
M
M
Igarashi
T
T
Fauci
A S
AS
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
D000939:Epitopes; D015483:HIV Antibodies; D009842:Oligopeptides; D019151:Peptide Library