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

PROBING THE PROMISCUITY OF THE HIV-1 NEUTRALIZING 2F5 ANTIBODY

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. MoAa0201

Julien J.-P., Bryson S., Pai E.F.
University of Toronto, Biochemistry, Toronto, Canada

BACKGROUND: The HIV-1 neutralizing antibody 2F5 recognizes an epitope consisting of amino acids 662-668 located at the membrane-proximal region of the gp41 protein, which is responsible for the membrane fusion mechanism of HIV-1. Thus far, efforts to induce an immunologic response by stimulating 2F5 antibody production from peptide-like molecules mimicking the β-turn structure of the antigen ELDKWAS have failed.

METHODS: In this study, the crystal structures of peptide molecules mutated, elongated and constrained at key positions of the ELDKWAS antigen in complex with the 2F5 antibody are studied.

RESULTS: It is observed from structures with and without peptide that three key waters are present around the epitope, which are thought to be important for antigen-antibody interaction. In addition, interpretation of the interactions at the C-terminus of the elongated antigen with the 2F5 antibody is limited because of crystal packing interactions that are present in that region. Finally, significant interactions of the side chains in the β-turn are identified from the mutated antigen structures, and results from mutations at the alanine 667 position are particularly interesting because they help in partially understanding the escape of clade C HIV-1 isolates from 2F5 neutralization.

CONCLUSIONS: The results presented here give new insights in the structure-based design of a peptide-like molecule potentially capable of stimulating 2F5 antibody production and help in the bigger quest of creating a potent vaccine for HIV-1.

Download PDF of this abstract.

2006-08-13
MoAa0201

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.