Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates
Summary: Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repet...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717301687 |
| _version_ | 1818245831288946688 |
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| author | Kevin O. Saunders Nathan I. Nicely Kevin Wiehe Mattia Bonsignori R. Ryan Meyerhoff Robert Parks William E. Walkowicz Baptiste Aussedat Nelson R. Wu Fangping Cai Yusuf Vohra Peter K. Park Amanda Eaton Eden P. Go Laura L. Sutherland Richard M. Scearce Dan H. Barouch Ruijun Zhang Tarra Von Holle R. Glenn Overman Kara Anasti Rogier W. Sanders M. Anthony Moody Thomas B. Kepler Bette Korber Heather Desaire Sampa Santra Norman L. Letvin Gary J. Nabel David C. Montefiori Georgia D. Tomaras Hua-Xin Liao S. Munir Alam Samuel J. Danishefsky Barton F. Haynes |
| author_facet | Kevin O. Saunders Nathan I. Nicely Kevin Wiehe Mattia Bonsignori R. Ryan Meyerhoff Robert Parks William E. Walkowicz Baptiste Aussedat Nelson R. Wu Fangping Cai Yusuf Vohra Peter K. Park Amanda Eaton Eden P. Go Laura L. Sutherland Richard M. Scearce Dan H. Barouch Ruijun Zhang Tarra Von Holle R. Glenn Overman Kara Anasti Rogier W. Sanders M. Anthony Moody Thomas B. Kepler Bette Korber Heather Desaire Sampa Santra Norman L. Letvin Gary J. Nabel David C. Montefiori Georgia D. Tomaras Hua-Xin Liao S. Munir Alam Samuel J. Danishefsky Barton F. Haynes |
| author_sort | Kevin O. Saunders |
| collection | DOAJ |
| description | Summary: Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans—a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors. : Most bnAb epitopes on HIV-1 Envelope include host glycans, but previous Env vaccines have not induced glycan-dependent antibodies. Saunders et al. describe here the ontogeny, crystal structure with glycan, and virion Man9GlcNAc2-dependent neutralization for glycan-reactive antibodies induced by envelope vaccination. Keywords: HIV, V3 glycan, vaccination, glycan, long-term immunization |
| first_indexed | 2024-12-12T14:39:10Z |
| format | Article |
| id | doaj.art-f020d40e9877461f93e8d9d15c7fa9e4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T14:39:10Z |
| publishDate | 2017-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f020d40e9877461f93e8d9d15c7fa9e42022-12-22T00:21:18ZengElsevierCell Reports2211-12472017-02-0118921752188Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman PrimatesKevin O. Saunders0Nathan I. Nicely1Kevin Wiehe2Mattia Bonsignori3R. Ryan Meyerhoff4Robert Parks5William E. Walkowicz6Baptiste Aussedat7Nelson R. Wu8Fangping Cai9Yusuf Vohra10Peter K. Park11Amanda Eaton12Eden P. Go13Laura L. Sutherland14Richard M. Scearce15Dan H. Barouch16Ruijun Zhang17Tarra Von Holle18R. Glenn Overman19Kara Anasti20Rogier W. Sanders21M. Anthony Moody22Thomas B. Kepler23Bette Korber24Heather Desaire25Sampa Santra26Norman L. Letvin27Gary J. Nabel28David C. Montefiori29Georgia D. Tomaras30Hua-Xin Liao31S. Munir Alam32Samuel J. Danishefsky33Barton F. Haynes34Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Corresponding authorDepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USASloan Kettering Institute for Cancer Research, New York, NY 10065, USASloan Kettering Institute for Cancer Research, New York, NY 10065, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USASloan Kettering Institute for Cancer Research, New York, NY 10065, USASloan Kettering Institute for Cancer Research, New York, NY 10065, USADepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USAUniversity of Kansas, Lawrence, KS 66045, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USACenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the NetherlandsDepartment of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USABoston University, Boston, MA 02215, USALANL, Los Alamos, NM 87545, USAUniversity of Kansas, Lawrence, KS 66045, USAHarvard Medical School, Boston, MA, 02215, USAHarvard Medical School, Boston, MA, 02215, USASanofi, Cambridge, MA 02139, USADepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USADepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USASloan Kettering Institute for Cancer Research, New York, NY 10065, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Corresponding authorSummary: Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans—a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors. : Most bnAb epitopes on HIV-1 Envelope include host glycans, but previous Env vaccines have not induced glycan-dependent antibodies. Saunders et al. describe here the ontogeny, crystal structure with glycan, and virion Man9GlcNAc2-dependent neutralization for glycan-reactive antibodies induced by envelope vaccination. Keywords: HIV, V3 glycan, vaccination, glycan, long-term immunizationhttp://www.sciencedirect.com/science/article/pii/S2211124717301687 |
| spellingShingle | Kevin O. Saunders Nathan I. Nicely Kevin Wiehe Mattia Bonsignori R. Ryan Meyerhoff Robert Parks William E. Walkowicz Baptiste Aussedat Nelson R. Wu Fangping Cai Yusuf Vohra Peter K. Park Amanda Eaton Eden P. Go Laura L. Sutherland Richard M. Scearce Dan H. Barouch Ruijun Zhang Tarra Von Holle R. Glenn Overman Kara Anasti Rogier W. Sanders M. Anthony Moody Thomas B. Kepler Bette Korber Heather Desaire Sampa Santra Norman L. Letvin Gary J. Nabel David C. Montefiori Georgia D. Tomaras Hua-Xin Liao S. Munir Alam Samuel J. Danishefsky Barton F. Haynes Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates Cell Reports |
| title | Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates |
| title_full | Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates |
| title_fullStr | Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates |
| title_full_unstemmed | Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates |
| title_short | Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates |
| title_sort | vaccine elicitation of high mannose dependent neutralizing antibodies against the v3 glycan broadly neutralizing epitope in nonhuman primates |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717301687 |
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