Selection of HIV-Specific Immunogenic Epitopes by Screening Random Peptide Libraries with HIV-1-Positive Sera

• Published in: The Journal of immunology (1950) Vol. 162; no. 10; pp. 6155 - 6161
• Main Authors: Scala, Giuseppe, Chen, Xueni, Liu, Weimin, Telles, Jean Noel, Cohen, Oren J, Vaccarezza, Mauro, Igarashi, Tatsu, Fauci, Anthony S
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.05.1999
• Subjects: Animals; Antibody Affinity; B-Lymphocytes - immunology; Epitopes; HIV Antibodies - blood; HIV Seropositivity - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Mice; Molecular Mimicry; Neutralization Tests; Oligopeptides - immunology; Peptide Library
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.162.10.6155

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.