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The Journal of Immunology, 1999, 162: 6155-6161.
Copyright © 1999 by The American Association of Immunologists

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

Giuseppe Scala1,2,*,{ddagger}, Xueni Chen1,*, Weimin Liu*, Jean Noel Telles*, Oren J. Cohen*, Mauro Vaccarezza*, Tatsu Igarashi{dagger} and Anthony S. Fauci*

* Laboratory of Immunoregulation, and {dagger} Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and {ddagger} Dipartimento di Medicina Sperimentale e Clinica, Universita‘ degli Studi di Catanzaro, Catanzaro, Italy

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.




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