Cell Reports (Nov 2021)
Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies
- Christopher A. Cottrell,
- Kartik Manne,
- Rui Kong,
- Shuishu Wang,
- Tongqing Zhou,
- Gwo-Yu Chuang,
- Robert J. Edwards,
- Rory Henderson,
- Katarzyna Janowska,
- Megan Kopp,
- Bob C. Lin,
- Mark K. Louder,
- Adam S. Olia,
- Reda Rawi,
- Chen-Hsiang Shen,
- Justin D. Taft,
- Jonathan L. Torres,
- Nelson R. Wu,
- Baoshan Zhang,
- Nicole A. Doria-Rose,
- Myron S. Cohen,
- Barton F. Haynes,
- Lawrence Shapiro,
- Andrew B. Ward,
- Priyamvada Acharya,
- John R. Mascola,
- Peter D. Kwong
Affiliations
- Christopher A. Cottrell
- IAVI Neutralizing Antibody Center, Consortium for HIV/AIDS Vaccine Development (CHAVD), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Kartik Manne
- Duke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USA
- Rui Kong
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Shuishu Wang
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Tongqing Zhou
- 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
- Robert J. Edwards
- Duke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USA
- Rory Henderson
- Duke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USA
- Katarzyna Janowska
- Duke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USA
- Megan Kopp
- Duke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, 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
- Adam S. Olia
- 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
- Chen-Hsiang Shen
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Justin D. Taft
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Jonathan L. Torres
- IAVI Neutralizing Antibody Center, Consortium for HIV/AIDS Vaccine Development (CHAVD), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Nelson R. Wu
- IAVI Neutralizing Antibody Center, Consortium for HIV/AIDS Vaccine Development (CHAVD), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Baoshan Zhang
- 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
- Myron S. Cohen
- Departments of Medicine, Epidemiology, and Microbiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA
- Barton F. Haynes
- Duke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USA
- Lawrence Shapiro
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
- Andrew B. Ward
- IAVI Neutralizing Antibody Center, Consortium for HIV/AIDS Vaccine Development (CHAVD), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Priyamvada Acharya
- Duke University Human Vaccine Institute, Departments of Medicine and Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- John R. Mascola
- 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; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Corresponding author
- Journal volume & issue
-
Vol. 37,
no. 5
p. 109922
Abstract
Summary: Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.
