Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes
Xueni Chen1, Giuseppe Scala1, 2, 3, Ileana Quinto1, 2, 3, Weimin Liu1, Tae-Wook Chun1, J. Shawn Justement1, Oren J. Cohen1, Tom C. vanCott4, Marcin Iwanicki4, Mark G. Lewis5, Jack Greenhouse5, Todd Barry6, David Venzon7
& Anthony S. Fauci1
1
Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, USA
2
Department of Clinical and Experimental Medicine, Medical School, University of Catanzaro, Catanzaro, Italy
3
Department of Biochemistry and Biomedical Technology, Medical School, University 'Federico II', Naples, Italy
4
H. M. Jackson Foundation, Rockville, Maryland, USA
5
Southern Research Institute, Frederick, Maryland, USA
6
Hematopathology Section, NCI, NIH, Bethesda, Maryland, USA
7
Biostatistics and Data Management Section, NCI, NIH, Bethesda, Maryland, USA
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.
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