Cell Reports (Dec 2024)
A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies
- Evan 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
Affiliations
- Evan M. Cale
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Chen-Hsiang Shen
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Adam S. Olia
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Nathan A. Radakovich
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Reda Rawi
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Yongping Yang
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- David R. Ambrozak
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Anthony K. Bennici
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Gwo-Yu Chuang
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Emma D. Crooks
- San Diego Biomedical Research Institute, San Diego, CA 92121, USA
- Jefferson I. Driscoll
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Bob C. Lin
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Mark K. Louder
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Patrick J. Madden
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Michael A. Messina
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Keiko Osawa
- San Diego Biomedical Research Institute, San Diego, CA 92121, USA
- Guillaume B.E. Stewart-Jones
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Raffaello Verardi
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Zoe Vrakas
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Danielle Xie
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Baoshan Zhang
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- James M. Binley
- San Diego Biomedical Research Institute, San Diego, CA 92121, USA
- Mark Connors
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Richard A. Koup
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Theodore C. Pierson
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Nicole A. Doria-Rose
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
- Peter D. Kwong
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Corresponding author
- John R. Mascola
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; ModeX Therapeutics, Weston, MA 02493, USA
- Jason Gorman
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 12
p. 115010
Abstract
Summary: 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.
