1. HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.
- Author
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Fera, Daniela, Lee, Matthew S., Wiehe, Kevin, Meyerhoff, R. Ryan, Piai, Alessandro, Bonsignori, Mattia, Aussedat, Baptiste, Walkowicz, William E., Ton, Therese, Zhou, Jeffrey O., Danishefsky, Samuel, Haynes, Barton F., and Harrison, Stephen C.
- Subjects
IMMUNOGLOBULINS ,VIRAL envelope proteins ,VACCINES ,HIV ,THERAPEUTICS - Abstract
HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide (“Man
9 -V3”) for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage (“DH270”), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9 -V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs—the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen. [ABSTRACT FROM AUTHOR]- Published
- 2018
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