Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth
Abstract
Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Furthermore, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.
- Authors:
- more »
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1410714
- Alternate Identifier(s):
- OSTI ID: 1338973
- Grant/Contract Number:
- W-31-109-Eng-38
- Resource Type:
- Published Article
- Journal Name:
- Immunity
- Additional Journal Information:
- Journal Name: Immunity Journal Volume: 45 Journal Issue: 5; Journal ID: ISSN 1074-7613
- Publisher:
- Cell Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; HIV; neutralizing; antibody; CD4-binding site; vaccine; immunotherapy; prophylaxis; resistance; envelope; structure
Citation Formats
Huang, Jinghe, Kang, Byong H., Ishida, Elise, Zhou, Tongqing, Griesman, Trevor, Sheng, Zizhang, Wu, Fan, Doria-Rose, Nicole A., Zhang, Baoshan, McKee, Krisha, O’Dell, Sijy, Chuang, Gwo-Yu, Druz, Aliaksandr, Georgiev, Ivelin S., Schramm, Chaim A., Zheng, Anqi, Joyce, M. Gordon, Asokan, Mangaiarkarasi, Ransier, Amy, Darko, Sam, Migueles, Stephen A., Bailer, Robert T., Louder, Mark K., Alam, S. Munir, Parks, Robert, Kelsoe, Garnett, Von Holle, Tarra, Haynes, Barton F., Douek, Daniel C., Hirsch, Vanessa, Seaman, Michael S., Shapiro, Lawrence, Mascola, John R., Kwong, Peter D., and Connors, Mark. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. United States: N. p., 2016.
Web. doi:10.1016/j.immuni.2016.10.027.
Huang, Jinghe, Kang, Byong H., Ishida, Elise, Zhou, Tongqing, Griesman, Trevor, Sheng, Zizhang, Wu, Fan, Doria-Rose, Nicole A., Zhang, Baoshan, McKee, Krisha, O’Dell, Sijy, Chuang, Gwo-Yu, Druz, Aliaksandr, Georgiev, Ivelin S., Schramm, Chaim A., Zheng, Anqi, Joyce, M. Gordon, Asokan, Mangaiarkarasi, Ransier, Amy, Darko, Sam, Migueles, Stephen A., Bailer, Robert T., Louder, Mark K., Alam, S. Munir, Parks, Robert, Kelsoe, Garnett, Von Holle, Tarra, Haynes, Barton F., Douek, Daniel C., Hirsch, Vanessa, Seaman, Michael S., Shapiro, Lawrence, Mascola, John R., Kwong, Peter D., & Connors, Mark. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. United States. https://doi.org/10.1016/j.immuni.2016.10.027
Huang, Jinghe, Kang, Byong H., Ishida, Elise, Zhou, Tongqing, Griesman, Trevor, Sheng, Zizhang, Wu, Fan, Doria-Rose, Nicole A., Zhang, Baoshan, McKee, Krisha, O’Dell, Sijy, Chuang, Gwo-Yu, Druz, Aliaksandr, Georgiev, Ivelin S., Schramm, Chaim A., Zheng, Anqi, Joyce, M. Gordon, Asokan, Mangaiarkarasi, Ransier, Amy, Darko, Sam, Migueles, Stephen A., Bailer, Robert T., Louder, Mark K., Alam, S. Munir, Parks, Robert, Kelsoe, Garnett, Von Holle, Tarra, Haynes, Barton F., Douek, Daniel C., Hirsch, Vanessa, Seaman, Michael S., Shapiro, Lawrence, Mascola, John R., Kwong, Peter D., and Connors, Mark. Tue .
"Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth". United States. https://doi.org/10.1016/j.immuni.2016.10.027.
@article{osti_1410714,
title = {Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth},
author = {Huang, Jinghe and Kang, Byong H. and Ishida, Elise and Zhou, Tongqing and Griesman, Trevor and Sheng, Zizhang and Wu, Fan and Doria-Rose, Nicole A. and Zhang, Baoshan and McKee, Krisha and O’Dell, Sijy and Chuang, Gwo-Yu and Druz, Aliaksandr and Georgiev, Ivelin S. and Schramm, Chaim A. and Zheng, Anqi and Joyce, M. Gordon and Asokan, Mangaiarkarasi and Ransier, Amy and Darko, Sam and Migueles, Stephen A. and Bailer, Robert T. and Louder, Mark K. and Alam, S. Munir and Parks, Robert and Kelsoe, Garnett and Von Holle, Tarra and Haynes, Barton F. and Douek, Daniel C. and Hirsch, Vanessa and Seaman, Michael S. and Shapiro, Lawrence and Mascola, John R. and Kwong, Peter D. and Connors, Mark},
abstractNote = {Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Furthermore, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.},
doi = {10.1016/j.immuni.2016.10.027},
journal = {Immunity},
number = 5,
volume = 45,
place = {United States},
year = {Tue Nov 01 00:00:00 EDT 2016},
month = {Tue Nov 01 00:00:00 EDT 2016}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1016/j.immuni.2016.10.027
https://doi.org/10.1016/j.immuni.2016.10.027
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 238 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Antibody responses to envelope glycoproteins in HIV-1 infection
journal, May 2015
- Burton, Dennis R.; Mascola, John R.
- Nature Immunology, Vol. 16, Issue 6
Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans
journal, December 2015
- Garces, Fernando; Lee, Jeong Hyun; de Val, Natalia
- Immunity, Vol. 43, Issue 6
Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site
journal, May 2015
- Crooks, Ema T.; Tong, Tommy; Chakrabarti, Bimal
- PLOS Pathogens, Vol. 11, Issue 5
Selection Pressure on HIV-1 Envelope by Broadly Neutralizing Antibodies to the Conserved CD4-Binding Site
journal, March 2012
- Wu, X.; Wang, C.; O'Dell, S.
- Journal of Virology, Vol. 86, Issue 10
Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo
journal, August 2014
- Rudicell, R. S.; Kwon, Y. D.; Ko, S. -Y.
- Journal of Virology, Vol. 88, Issue 21
Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G
journal, May 2016
- Stewart-Jones, Guillaume B. E.; Soto, Cinque; Lemmin, Thomas
- Cell, Vol. 165, Issue 4
Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies
journal, July 2014
- Gao, Feng; Bonsignori, Mattia; Liao, Hua-Xin
- Cell, Vol. 158, Issue 3
Rapid development of broadly influenza neutralizing antibodies through redundant mutations
journal, October 2014
- Pappas, Leontios; Foglierini, Mathilde; Piccoli, Luca
- Nature, Vol. 516, Issue 7531
Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design
journal, October 2011
- Diskin, R.; Scheid, J. F.; Marcovecchio, P. M.
- Science, Vol. 334, Issue 6060
Restricting HIV-1 pathways for escape using rationally designed anti–HIV-1 antibodies
journal, May 2013
- Diskin, Ron; Klein, Florian; Horwitz, Joshua A.
- The Journal of Experimental Medicine, Vol. 210, Issue 6
Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization
journal, May 2013
- Georgiev, I. S.; Doria-Rose, N. A.; Zhou, T.
- Science, Vol. 340, Issue 6133
Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape
journal, October 2012
- Moore, Penny L.; Gray, Elin S.; Wibmer, C. Kurt
- Nature Medicine, Vol. 18, Issue 11
Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm
journal, May 2009
- Simek, M. D.; Rida, W.; Priddy, F. H.
- Journal of Virology, Vol. 83, Issue 14
Antibody engineering for increased potency, breadth and half-life
journal, January 2015
- Sievers, Stuart A.; Scharf, Louise; West, Anthony P.
- Current Opinion in HIV and AIDS, Vol. 10, Issue 3
Rapid evolution of the neutralizing antibody response to HIV type 1 infection
journal, March 2003
- Richman, D. D.; Wrin, T.; Little, S. J.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 7
Mechanism of Neutralization by the Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01
journal, June 2011
- Li, Y.; O'Dell, S.; Walker, L. M.
- Journal of Virology, Vol. 85, Issue 17
Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables
journal, November 2009
- Doria-Rose, N. A.; Klein, R. M.; Daniels, M. G.
- Journal of Virology, Vol. 84, Issue 3
Determinants of HIV-1 broadly neutralizing antibody induction
journal, September 2016
- Rusert, Peter; Kouyos, Roger D.; Kadelka, Claus
- Nature Medicine, Vol. 22, Issue 11
Structure of the Epstein-Barr virus major envelope glycoprotein
journal, October 2006
- Szakonyi, Gerda; Klein, Michael G.; Hannan, Jonathan P.
- Nature Structural & Molecular Biology, Vol. 13, Issue 11
Broadly Neutralizing Antibodies for HIV Eradication
journal, February 2016
- Stephenson, Kathryn E.; Barouch, Dan H.
- Current HIV/AIDS Reports, Vol. 13, Issue 1
Antibody neutralization and escape by HIV-1
journal, March 2003
- Wei, Xiping; Decker, Julie M.; Wang, Shuyi
- Nature, Vol. 422, Issue 6929
Viral Escape from HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition of Multiple Epitopes and Immunotypes
journal, October 2013
- Wibmer, Constantinos Kurt; Bhiman, Jinal N.; Gray, Elin S.
- PLoS Pathogens, Vol. 9, Issue 10
Isolation of human monoclonal antibodies from peripheral blood B cells
journal, September 2013
- Huang, Jinghe; Doria-Rose, Nicole A.; Longo, Nancy S.
- Nature Protocols, Vol. 8, Issue 10
Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants
journal, November 2014
- Klein, Florian; Nogueira, Lilian; Nishimura, Yoshiaki
- The Journal of Experimental Medicine, Vol. 211, Issue 12
Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain
journal, November 2010
- Das, Suman R.; Puigbò, Pere; Hensley, Scott E.
- PLoS Pathogens, Vol. 6, Issue 11
Factors Associated with the Development of Cross-Reactive Neutralizing Antibodies during Human Immunodeficiency Virus Type 1 Infection
journal, November 2008
- Sather, D. N.; Armann, J.; Ching, L. K.
- Journal of Virology, Vol. 83, Issue 2
Role of N-Linked Glycans in the Functions of Hepatitis C Virus Envelope Proteins Incorporated into Infectious Virions
journal, September 2010
- Helle, F.; Vieyres, G.; Elkrief, L.
- Journal of Virology, Vol. 84, Issue 22
Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors
journal, June 2015
- Zhou, Tongqing; Lynch, Rebecca M.; Chen, Lei
- Cell, Vol. 161, Issue 6
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies
journal, March 2014
- Doria-Rose, Nicole A.; Schramm, Chaim A.; Gorman, Jason
- Nature, Vol. 509, Issue 7498
New approaches to HIV vaccine development
journal, August 2015
- Haynes, Barton F.
- Current Opinion in Immunology, Vol. 35
Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection
journal, November 2015
- Sommerstein, Rami; Flatz, Lukas; Remy, Melissa M.
- PLOS Pathogens, Vol. 11, Issue 11
HIV-1 Fitness Cost Associated with Escape from the VRC01 Class of CD4 Binding Site Neutralizing Antibodies
journal, January 2015
- Lynch, Rebecca M.; Wong, Patrick; Tran, Lillian
- Journal of Virology, Vol. 89, Issue 8
Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection
journal, April 2015
- Wu, Xueling; Zhang, Zhenhai; Schramm, Chaim A.
- Cell, Vol. 161, Issue 3
Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies
journal, July 2005
- Li, M.; Gao, F.; Mascola, J. R.
- Journal of Virology, Vol. 79, Issue 16
Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch
journal, May 2016
- MacLeod, Daniel T.; Choi, Nancy M.; Briney, Bryan
- Immunity, Vol. 44, Issue 5
Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies
journal, August 2013
- Zhou, Tongqing; Zhu, Jiang; Wu, Xueling
- Immunity, Vol. 39, Issue 2
Molecular Evolution and Circulation Patterns of Human Respiratory Syncytial Virus Subgroup A: Positively Selected Sites in the Attachment G Glycoprotein
journal, May 2004
- Zlateva, Kalina T.; Lemey, Philippe; Vandamme, Anne-Mieke
- Journal of Virology, Vol. 78, Issue 9
Polyreactivity and Autoreactivity among HIV-1 Antibodies
journal, October 2014
- Liu, Mengfei; Yang, Guang; Wiehe, Kevin
- Journal of Virology, Vol. 89, Issue 1