Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination

Author:  ["Xueni Chen","Giuseppe Scala","Ileana Quinto","Weimin Liu","Tae-Wook Chun","J. Shawn Justement","Oren J. Cohen","Tom C. vanCott","Marcin Iwanicki","Mark G. Lewis","Jack Greenhouse","Todd Barry","David Venzon","Anthony S. Fauci"]

Publication:  Nature Medicine

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Tags:     Medicine

Abstract

The antigenic polymorphism of HIV-1 is a major obstacle in developing an effective vaccine. Accordingly, we screened random peptide libraries (RPLs) displayed on phage with antibodies from HIV-infected individuals and identified an array of HIV-specific epitopes that behave as antigenic mimics of conformational epitopes of gp120 and gp41 proteins. We report that the selected epitopes are shared by a collection of HIV-1 isolates of clades A–F. The phage-borne epitopes are immunogenic in rhesus macaques, where they elicit envelope-specific antibody responses. Upon intravenous challenge with 60 MID50 of pathogenic SHIV-89.6PD, all monkeys became infected; however, in contrast to the naive and mock-immunized monkeys, four of five mimotope-immunized monkeys experienced lower levels of peak viremia, followed by viral set points of undetectable or transient levels of viremia and a mild decline of CD4+ T cells, and were protected from progression to AIDS-like illness. These results provide a new approach to the design of broadly protective HIV-1 vaccines.

Cite this article

Chen, X., Scala, G., Quinto, I. et al. Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes. Nat Med 7, 1225–1231 (2001). https://doi.org/10.1038/nm1101-1225

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