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PLoS One. 2014 Feb 25;9(2):e89987. doi: 10.1371/journal.pone.0089987. eCollection 2014.

Computational prediction of neutralization epitopes targeted by human anti-V3 HIV monoclonal antibodies.

Author information

1
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
2
Public Health Research Institute Center, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
3
Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, New York, United States of America.

Abstract

The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs) can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs). Our data demonstrate that this approach, based purely on calculated energetics and 3D structural information, accurately predicts the presence of neutralization epitopes targeted by V3-specific mAbs 2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range of conservation of these specific epitopes across all circulating HIV-1 viruses. Accurately identifying an Ab-targeted neutralization epitope in a virus by computational means enables easy prediction of the breadth of reactivity of specific mAbs across the diversity of thousands of different circulating HIV-1 variants and facilitates rational design and selection of immunogens mimicking specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined epitopes can also be used for the purpose of epitope-specific analyses of breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a prototype for a valuable tool for rational HIV-1 vaccine design.

PMID:
24587168
PMCID:
PMC3934971
DOI:
10.1371/journal.pone.0089987
[Indexed for MEDLINE]
Free PMC Article

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