HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.

Autor: Fera D; Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA. dfera1@swarthmore.edu., Lee MS; Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Wiehe K; Department of Medicine, Duke University School of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.; Duke Human Vaccine Institute, Durham, NC, 27710, USA., Meyerhoff RR; Duke Human Vaccine Institute, Durham, NC, 27710, USA.; Department of Immunology, Duke University School of Medicine, Duke University Medical Center, Durham, NC, 27710, USA., Piai A; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA., Bonsignori M; Department of Medicine, Duke University School of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.; Duke Human Vaccine Institute, Durham, NC, 27710, USA., Aussedat B; Department of Bioorganic Chemistry, Sloan Kettering Institute, New York, NY, 10065, USA., Walkowicz WE; Department of Bioorganic Chemistry, Sloan Kettering Institute, New York, NY, 10065, USA., Ton T; Department of Biology, Swarthmore College, Swarthmore, PA, 19081, USA., Zhou JO; Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA, 19081, USA., Danishefsky S; Department of Bioorganic Chemistry, Sloan Kettering Institute, New York, NY, 10065, USA., Haynes BF; Department of Medicine, Duke University School of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.; Duke Human Vaccine Institute, Durham, NC, 27710, USA., Harrison SC; Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, 02115, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Mar 16; Vol. 9 (1), pp. 1111. Date of Electronic Publication: 2018 Mar 16.
DOI: 10.1038/s41467-018-03565-6
Abstrakt: 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, Man 9 -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.
Databáze: MEDLINE