16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

VACCINE-RELEVANT MIMOTOPES SELECTED WITH NEUTRALIZING IGG PRESENT IN PLASMA FROM LONG-TERM NON-PROGRESSORS (LTNP) BY PHAGE DISPLAY

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. MoAa0204

Humbert M.¹, Antoni S.¹, Landersz M.¹, Rodes B.², Soriano V.², Knechten H.³, Staszewski S.⁴, von Laer D.¹, Dittmar M.⁵, Dietrich U.^1
1Georg-Speyer-Haus, Molecular Virology, Frankfurt, Germany, ²Instituto de Salud Carlos III, Madrid, Spain, ³Praxiszentrum Blondelstr., Aachen, Germany, ⁴JW Goethe University Hospital, Division of Infectious Diseases, Frankfurt, Germany, ⁵Hygiene Institute, Virology, Heidelberg, Germany

BACKGROUND: Non-progressive disease is a hallmark of LTNPs and the underlying control mechanisms are multifactorial including viral, cellular and immunological factors. Here we focus on the role of neutralizing antibodies for the LTNP status and aim at the identification of the corresponding epitopes as potential vaccine candidates.

METHODS: Neutralizing antibodies in our LTNP sera were detected by in vitro neutralization assays using recombinant repoter HIV-1 and U87-CCR5/CXCR4 cells. For the biopannings, LTNP IgG were immobilized and screened with 3 phage displayed peptide libraries. After several rounds of positive and negative selection, mimotopes were tested by ELISA for specificity. Sequences of peptide inserts were determined and analyzed for homology to HIV-1 proteins by 3DEX, a program we developed for the identification of conformational epitopes. Phages grouped according to peptide similarity were used for immunizations of mice to prove the induction of neutralizing antibodies against HIV-1 by the selected mimotopes.

RESULTS: Our LTNP sera contained broadly neutralizing antibodies against HIV-1 with titers significantly higher than those in control sera. More than 1400 phage clones selected with LTNP IgG were analyzed by ELISA, more than 700 phage inserts were sequenced. We could identify motifs corresponding to the immunodominant epitopes in HIV-1 Env, but also interesting conformational epitopes overlapping with receptor binding sites on the surface of gp120. Sera from mice immunized with ceratin phage groups showed neutralizing activity against HIV-1 in vitro proving that the phage mimotopes indeed mimic epitopes for neutralizing antibodies.

CONCLUSIONS: The phage display technology was successfully applied to identify HIV-1 specific mimotopes for neutralizing antibodies supposed to have a protective role in LTNP. These mimotopes represent candidates for the derivation of vaccine-relevant immunogens.

This work is supported by the Deutsche Forschungsgemeinschaft, the German AIDS research award and the Dr. Bodo Sponholz-Stiftung.

Download PDF of this abstract.

2006-08-13
MoAa0204

Copyright © 2006 - International AIDS Society (IAS). All information and content relating to the abstracts from the 16th International AIDS Conference, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is a 501c(3) not-for-profit organization made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, GlaxoSmithKline, the National Library of Medicine, Roche / Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 2006. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2006. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.