Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike
Broadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, are currently limited. We defined a new site of vulnerability by solving structures of bNAb 8ANC195 com...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714002848 |
| _version_ | 1818692684115607552 |
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| author | Louise Scharf Johannes F. Scheid Jeong Hyun Lee Anthony P. West Jr. Courtney Chen Han Gao Priyanthi N.P. Gnanapragasam René Mares Michael S. Seaman Andrew B. Ward Michel C. Nussenzweig Pamela J. Bjorkman |
| author_facet | Louise Scharf Johannes F. Scheid Jeong Hyun Lee Anthony P. West Jr. Courtney Chen Han Gao Priyanthi N.P. Gnanapragasam René Mares Michael S. Seaman Andrew B. Ward Michel C. Nussenzweig Pamela J. Bjorkman |
| author_sort | Louise Scharf |
| collection | DOAJ |
| description | Broadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, are currently limited. We defined a new site of vulnerability by solving structures of bNAb 8ANC195 complexed with monomeric gp120 by X-ray crystallography and trimeric Env by electron microscopy. The site includes portions of gp41 and N-linked glycans adjacent to the CD4-binding site on gp120, making 8ANC195 the first donor-derived anti-HIV-1 bNAb with an epitope spanning both Env subunits. Rather than penetrating the glycan shield by using a single variable-region CDR loop, 8ANC195 inserted its entire heavy-chain variable domain into a gap to form a large interface with gp120 glycans and regions of the gp120 inner domain not contacted by other bNAbs. By isolating additional 8ANC195 clonal variants, we identified a more potent variant, which may be valuable for therapeutic approaches using bNAb combinations with nonoverlapping epitopes. |
| first_indexed | 2024-12-17T13:01:42Z |
| format | Article |
| id | doaj.art-b45bc7f778fe44cd8a6b8622b264d5cc |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-17T13:01:42Z |
| publishDate | 2014-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b45bc7f778fe44cd8a6b8622b264d5cc2022-12-21T21:47:20ZengElsevierCell Reports2211-12472014-05-017378579510.1016/j.celrep.2014.04.001Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope SpikeLouise Scharf0Johannes F. Scheid1Jeong Hyun Lee2Anthony P. West Jr.3Courtney Chen4Han Gao5Priyanthi N.P. Gnanapragasam6René Mares7Michael S. Seaman8Andrew B. Ward9Michel C. Nussenzweig10Pamela J. Bjorkman11Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USALaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USABeth Israel Deaconess Medical Center, Boston, MA 02215, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USALaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USABroadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, are currently limited. We defined a new site of vulnerability by solving structures of bNAb 8ANC195 complexed with monomeric gp120 by X-ray crystallography and trimeric Env by electron microscopy. The site includes portions of gp41 and N-linked glycans adjacent to the CD4-binding site on gp120, making 8ANC195 the first donor-derived anti-HIV-1 bNAb with an epitope spanning both Env subunits. Rather than penetrating the glycan shield by using a single variable-region CDR loop, 8ANC195 inserted its entire heavy-chain variable domain into a gap to form a large interface with gp120 glycans and regions of the gp120 inner domain not contacted by other bNAbs. By isolating additional 8ANC195 clonal variants, we identified a more potent variant, which may be valuable for therapeutic approaches using bNAb combinations with nonoverlapping epitopes.http://www.sciencedirect.com/science/article/pii/S2211124714002848 |
| spellingShingle | Louise Scharf Johannes F. Scheid Jeong Hyun Lee Anthony P. West Jr. Courtney Chen Han Gao Priyanthi N.P. Gnanapragasam René Mares Michael S. Seaman Andrew B. Ward Michel C. Nussenzweig Pamela J. Bjorkman Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike Cell Reports |
| title | Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike |
| title_full | Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike |
| title_fullStr | Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike |
| title_full_unstemmed | Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike |
| title_short | Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike |
| title_sort | antibody 8anc195 reveals a site of broad vulnerability on the hiv 1 envelope spike |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714002848 |
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