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TitleA multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies.
Journal, issue, pagesCell Rep, Vol. 43, Issue 12, Page 115010, Year 2024
Publish dateDec 24, 2024
AuthorsEvan M Cale / Chen-Hsiang Shen / Adam S Olia / Nathan A Radakovich / Reda Rawi / Yongping Yang / David R Ambrozak / Anthony K Bennici / Gwo-Yu Chuang / Emma D Crooks / Jefferson I Driscoll / Bob C Lin / Mark K Louder / Patrick J Madden / Michael A Messina / Keiko Osawa / Guillaume B E Stewart-Jones / Raffaello Verardi / Zoe Vrakas / Danielle Xie / Baoshan Zhang / James M Binley / Mark Connors / Richard A Koup / Theodore C Pierson / Nicole A Doria-Rose / Peter D Kwong / John R Mascola / Jason Gorman /
PubMed AbstractAntibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize ...Antibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize VRC44, a bNAb lineage with up to 52% neutralization breadth. The cryoelectron microscopy (cryo-EM) structure of antibody VRC44.01 in complex with the Env trimer reveals binding to the same gp120-gp41 interface site of vulnerability as antibody 35O22 from a different HIV-1-infected donor. In addition to having similar angles of approach and extensive contacts with glycans N88 and N625, VRC44 and 35O22 derive from the same IGHV1-18 gene and share convergent mutations, indicating these two antibodies to be members of the only known highly glycan-dependent multidonor class. Strikingly, both lineages achieved almost 100% neutralization breadth against virus strains displaying high-mannose glycans. The high breadth and reproducible elicitation of VRC44 and 35O22 lineages validate germline-based methods of immunogen design for targeting the HIV-1 gp120-gp41 interface.
External linksCell Rep / PubMed:39675002
MethodsEM (single particle)
Resolution2.83 Å
Structure data

44595

9bio

EMDB-44595, PDB-9bio:
Structure of VRC44.01 Fab in complex with 3BNC117-purified C1080.c3 RnS SOSIP.664 HIV-1 Env trimer
Method: EM (single particle) / Resolution: 2.83 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-PO4:
PHOSPHATE ION

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / SOSIP / Vaccine / therapeutic / VIRAL PROTEIN-IMMUNE SYSTEM complex / subunit / multi-donor

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