Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10

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4E10 is an antibody that neutralizes a broad variety of HIV strains. However, 4E10 is uncommon in infected patients and has not been successfully elicited by any vaccine approach attempted. Hurdles to re-eliciting 4E10 include the accumulation of many mutations during development, demonstrated reactivity against host proteins and significant structural flexibility. Lacking a confirmed sequence for precursors of 4E10, we studied the recognition and biophysical properties of an ensemble of eight of the likeliest candidates. Surprisingly, 4E10 gained host reactivity and structural flexibility, but lost stability during development when compared to candidate precursors. However, recognition of HIV was remarkably conserved, despite a considerable improvement in binding. Since these results run counter to those expected from conventional vaccination protocols, 4E10 is unlikely to serve as the basis of a useful HIV vaccine.

Vyšlo v časopise: Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004403
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004403

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