Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/94372
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Type: Journal article
Title: Designer antigens for elicitation of broadly neutralizing antibodies against HIV
Author: Kok, T.
Gaeguta, A.
Finnie, J.
Gorry, P.
Churchill, M.
Li, P.
Citation: Clinical and Translational Immunology, 2014; 3(9):e24-1-e24-6
Publisher: Nature
Issue Date: 2014
ISSN: 2050-0068
2050-0068
Statement of
Responsibility: 
Tuckweng Kok, Adriana Gaeguta, John Finnie, Paul R Gorry, Melissa Churchill, and Peng Li
Abstract: Broadly neutralizing antibodies (bNAbs) are a consistent protective immune correlate in human immunodeficiency virus (HIV) patients as well as in passive immunotherapy studies. The inability to elicit bNAbs is the core reason underlining the repeated failures in traditional HIV vaccine research. Rare monoclonal bNAbs against HIV, however, have been produced. The significance of producing and studying more monoclonal bNAbs against HIV is underlined by its capability of defining critical epitopes for antigen designs aimed at the development of a serum-neutralizing HIV vaccine. In this regard, traditional antigen preparations have failed. There is a need to clearly advocate the concept, and systematic study, of more sophisticated 'designer antigens' (DAGs), which carry epitopes that can lead to the elicitation of bNAbs. Using an extremely efficient cell-to-cell HIV infection model for the preparation of HIV prefusion intermediates, we have investigated a novel and systematic approach to produce (not screen for) potential bNAbs against HIV. We have established the concept and the experimental system for producing formaldehyde-fixed HIV DAGs that carry temperature-arrested prefusion intermediates. These prefusion intermediates are structures on the cell surface after viral attachment and receptor engagement but before fully functional viral entry. Using defined HIV prefusion DAGs, we have produced monoclonal antibodies (mAbs) specific to novel epitopes on HIV prefusion intermediates. These mAbs do not react with the static/native surface HIV or cellular antigens, but react with the DAGs. This is a paradigm shift from the current mainstream approach of screening elite patients' bNAbs.
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
DOI: 10.1038/cti.2014.22
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