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Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core.

eLife | 2018

VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4BS) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding VRC01 germline precursors poorly bind to Env. Immunogen design has mostly relied on glycan removal from trimeric Env constructs and has had limited success in eliciting mature VRC01 bnAbs. To better understand elicitation of such bnAbs, we characterized the inferred germline precursor of VRC01 in complex with a modified trimeric 426c Env by cryo-electron microscopy and a 426c gp120 core by X-ray crystallography, biolayer interferometry, immunoprecipitation, and glycoproteomics. Our results show VRC01 germline antibodies interacted with a wild-type 426c core lacking variable loops 1-3 in the presence and absence of a glycan at position Asn276, with the latter form binding with higher affinity than the former. Interactions in the presence of an Asn276 oligosaccharide could be enhanced upon carbohydrate shortening, which should be considered for immunogen design.

Pubmed ID: 30403372 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

Antibodies used in this publication

None found

Associated grants

  • Agency: National Institute of Allergy and Infectious Diseases, International
    Id: U19 AI109632
  • Agency: National Institute of Allergy and Infectious Diseases, International
    Id: P01 AI094419
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM120553
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI109632
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI081625
  • Agency: National Institute of Allergy and Infectious Diseases, International
    Id: R01AI081625
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM120553
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM123089
  • Agency: NIH HHS, United States
    Id: S10 OD018111
  • Agency: NIGMS NIH HHS, United States
    Id: T32GM008268
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI104384
  • Agency: NIGMS NIH HHS, United States
    Id: U24 GM116792
  • Agency: National Institute of Allergy and Infectious Diseases, International
    Id: R01 AI104384
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR023057
  • Agency: National Institute of Allergy and Infectious Diseases, International
    Id: R01 AI081625
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008268
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI094419

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RRID:SCR_016733

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RRID:CVCL_A785

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View all literature mentions