A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies
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.
Authors
- Raffaello Verardi (ORCID: https://orcid.org/0000-0002-2613-1223)
- Guillaume B. E. Stewart-Jones (ORCID: https://orcid.org/0000-0002-2440-3790)
- Bob C. Lin (ORCID: https://orcid.org/0000-0002-1373-1406)
- Jason Gorman (ORCID: https://orcid.org/0000-0002-3775-6560)
- Richard A. Koup (ORCID: https://orcid.org/0000-0002-3090-7282)
- James Μ. Binley (ORCID: https://orcid.org/0000-0001-5032-6111)
- Adam S. Olia (ORCID: https://orcid.org/0000-0003-0805-1331)
- Danielle Xie (ORCID: https://orcid.org/0000-0001-6140-8171)
- Yongping Yang (ORCID: https://orcid.org/0000-0002-8307-1095)
- David R. Ambrozak (ORCID: https://orcid.org/0000-0003-1038-7328)
- Mark Connors (ORCID: https://orcid.org/0000-0002-2108-8705)
- Jefferson I. Driscoll
- Anthony K. Bennici
- Keiko Osawa
- Peter D. Kwong (ORCID: https://orcid.org/0000-0003-3560-232X)
- Theodore C. Pierson (ORCID: https://orcid.org/0000-0002-3795-4348)
- Nathan A. Radakovich
- Patrick Madden (ORCID: https://orcid.org/0000-0003-4527-5692)
- Mark K. Louder (ORCID: https://orcid.org/0000-0001-7540-9263)
- Gwo‐Yu Chuang (ORCID: https://orcid.org/0000-0003-0375-1013)
- Evan M. Cale (ORCID: https://orcid.org/0000-0002-9176-8263)
- John R. Mascola (ORCID: https://orcid.org/0000-0002-5293-4695)
- Chen‐Hsiang Shen (ORCID: https://orcid.org/0000-0002-9560-3992)
- Michael A. Messina
- Nicole A. Doria‐Rose (ORCID: https://orcid.org/0000-0002-5731-3054)
- Reda Rawi (ORCID: https://orcid.org/0000-0002-0445-2325)
- Baoshan Zhang (ORCID: https://orcid.org/0000-0002-0165-1513)
- Emma D Crooks
- Zoe Vrakas
Institutions
- National Institutes of Health (US)
- Center for Biologics Evaluation and Research (US)
- San Diego Biomedical Research Institute (US)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.115010
- Citations
- 6
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.76