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Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.
Pubmed ID: 23552890 RIS Download
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A user-sponsored molecular visualization software system on an open-source foundation. The software has the capabilities to view, render, animate, export, present and develop three dimensional molecular structures.
View all literature mentionsContains comprehensive data on HIV genetic sequences and immunological epitopes. This collection of databases contains tools to visualize and analyze HIV-related data.
View all literature mentionsNon-profit academic organization for research and services in bioinformatics. Provides freely available data from life science experiments, performs basic research in computational biology, and offers user training programme, manages databases of biological data including nucleic acid, protein sequences, and macromolecular structures. Part of EMBL.
View all literature mentionsElectronic archive and distribution server for research articles providing open access to more than 850,000 e-prints in Physics, Mathematics, Computer Science, Quantitative Biology, Quantitative Finance and Statistics. Users can retrieve papers via the web interface. Registered authors may use the web interface to submit their articles to arXiv. Authors can also update their submissions if they choose, though previous versions remain available. Listings of newly submitted articles in areas of interest are available via the web interface, via RSS feeds, and by subscription to automatic email alerts.
View all literature mentionsA free package of software programs for inferring phylogenies (evolutionary trees). The source code is distributed (in C), and executables are also distributed. In particular, already-compiled executables are available for Windows (95/98/NT/2000/me/xp/Vista), Mac OS X, and Linux systems. Older executables are also available for Mac OS 8 or 9 systems.
View all literature mentionsCell line U-118MG is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEp-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293-F is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets HIV-1 Envelope CD4 binding site
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