8th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 4 - 8, 2001



Rhesus macaques vaccinated with phage-displayed HIV-1 epitopes and subsequently infected with SHIV-89.6PD are partially protected against disease progression

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:50 (abstract no. 26)

X. Chen1, G. Scala1, W. Liu1, I. Quinto1, O. J. Cohen1, T. C. Van Cott2, M. Iwanicki2, M. Lewis3, D. C. Montefiori4, and A. S. Fauci1
1NIH, Bethesda, MD; 2H. M. Jackson Fndn., Rockville, MD; 3Southern Res. Inst., Frederick, MD; and 4Duke Univ., Durham, NC.



METHODS: To identify HIV-specific epitopes, we screened random peptide libraries (RPL) displayed on phages by using HIV-positive sera.

RESULTS: By several criteria, these peptides behaved as antigenic mimics of conformational B-cell epitopes generated in vivo in the course of the natural HIV-1 infection. Consistent with these findings, sera of monkeys infected with SHIVs carrying envelopes from different primary isolates, such as DH12, 89.6 and 89.6P, also recognized the pool of HIV-specific epitopes (G. Scala et al., J Immunol. 1999 May 15;162(10):6155-61). When injected in a group of five rhesus macaques with QS21 adjuvant, a pool of five epitopes induced an antibody response specific for each of the single epitopes, and this response cross-reacted with HIV-1 envelope proteins in three monkeys. The mimotope-immunized animals, together with a control group of four monkeys immunized with wild-type phages and a group of three naïve animals, were challenged i.v. with 60 AID50 of SHIV-89.6PD. During three months of observation, monkeys in the control groups experienced high peaks of viremia, an irreversible decline of CD4 T cells and AIDS-like syndromes. The mimotope-immunized monkeys were unprotected from primary infection; however, three out of five animals showed reduced levels of peak viremia with low or undetectable levels thereafter and a sustained number of CD4+ T cells (ranging between 20% and 40% of the pre-challenge levels) in the absence of abnormal clinical parameters.

CONCLUSION: The results suggest that phage-displayed epitopes may serve as a new approach in designing HIV-1.

2001-02-04
26

Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.