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

Journal Article · · Nature Communications
 [1];  [1];  [2];  [3];  [1];  [2];  [4];  [4];  [5];  [5];  [4];  [2];  [1]
  1. Harvard Medical School, Boston, MA (United States)
  2. Duke Univ. Medical Center, Durham, NC (United States); Duke Human Vaccine Inst., Durham, NC (United States)
  3. Duke Human Vaccine Inst., Durham, NC (United States); Duke Univ. Medical Center, Durham, NC (United States)
  4. Sloan Kettering Institute, New York, NY (United States)
  5. Swarthmore College, PA (United States)
+ Show Author Affiliations
HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide (“Man9-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.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
Medical Scientist Training Program (MSTP); NIH; NIH-ORIP HEI; National Inst. of Allergy and Infectious Diseases; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1431358
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 9; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (6)

The Impact of Sustained Immunization Regimens on the Antibody Response to Oligomannose Glycans journal February 2020
Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants journal April 2020
The Effects of Framework Mutations at the Variable Domain Interface on Antibody Affinity Maturation in an HIV-1 Broadly Neutralizing Antibody Lineage journal July 2020
Glycopeptides and -Mimetics to Detect, Monitor and Inhibit Bacterial and Viral Infections: Recent Advances and Perspectives journal March 2019
Targeted selection of HIV-specific antibody mutations by engineering B cell maturation journal December 2019
Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers journal September 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Antibodies
HIV infections
Structural biology
Vaccines