Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
Xueling Wu,Zhi Yong Yang,Yuxing Li,Carl Magnus Hogerkorp,William R. Schief,Michael S. Seaman,Tongqing Zhou,Stephen D. Schmidt,Lan Wu,Ling Xu,Nancy S. Longo,Krisha McKee,Sijy O'Dell,Mark K. Louder,Diane Wycuff,Yu Feng,Martha Nason,Nicole A. Doria-Rose,Mark Connors,Peter D. Kwong,Mario Roederer,Richard T. Wyatt,Gary J. Nabel,John R. Mascola +23 more
Reads0
Chats0
TLDR
Three broadly neutralizing antibodies are identified, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike.Abstract:
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.read more
Citations
More filters
Journal ArticleDOI
Passive immunotherapy of viral infections: 'super-antibodies' enter the fray.
TL;DR: The next few years will be decisive in the realization of the promise of super-antibodies for the prophylaxis and therapy of infections with a range of viruses, including those that is highly antigenically variable and those that are newly emerging or that have pandemic potential.
Journal ArticleDOI
A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite
Neville K. Kisalu,Azza H. Idris,Connor Weidle,Yevel Flores-Garcia,Barbara J. Flynn,Brandon K. Sack,Sean C. Murphy,Arne Schön,Ernesto Freire,Joseph R. Francica,Alex B. Miller,Jason Gregory,Sandra March,Hua-Xin Liao,Barton F. Haynes,Kevin Wiehe,Ashley M. Trama,Kevin O. Saunders,Morgan A. Gladden,Anthony Monroe,Mattia Bonsignori,Masaru Kanekiyo,Adam K. Wheatley,Adrian B. McDermott,S. Katie Farney,Gwo-Yu Chuang,Baoshan Zhang,Natasha Kc,Sumana Chakravarty,Peter D. Kwong,Photini Sinnis,Sangeeta N. Bhatia,Stefan H. I. Kappe,B. Kim Lee Sim,Stephen L. Hoffman,Fidel Zavala,Marie Pancera,Robert A. Seder +37 more
TL;DR: The demonstration that CIS43 is highly effective for passive prevention of malaria has potential application for use in travelers, military personnel and elimination campaigns and identifies a new and conserved site of vulnerability on PfCSP for next-generation rational vaccine design.
Journal ArticleDOI
Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers
Talar Tokatlian,Benjamin J. Read,Christopher A. Jones,Daniel W. Kulp,Daniel W. Kulp,Daniel W. Kulp,Sergey Menis,Sergey Menis,Jason Y. Chang,Jon M. Steichen,Jon M. Steichen,Sudha Kumari,Joel D. Allen,Eric L. Dane,Alessia Liguori,Maya Sangesland,Daniel Lingwood,Max Crispin,William R. Schief,Darrell J. Irvine +19 more
TL;DR: These findings identify an innate immune–mediated recognition pathway promoting antibody responses to particulate antigens, with broad implications for humoral immunity and vaccine design.
Journal ArticleDOI
Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals
Georgia D. Tomaras,James M. Binley,Elin S. Gray,Emma T. Crooks,Keiko Osawa,Penny L. Moore,Nancy Tumba,Tommy Tong,Xiaoying Shen,Nicole L. Yates,Julie Decker,Constantinos Kurt Wibmer,Feng Gao,S. Munir Alam,Philippa Easterbrook,Salim S. Abdool Karim,Gift Kamanga,John A. Crump,Myron S. Cohen,George M. Shaw,John R. Mascola,Barton F. Haynes,David C. Montefiori,Lynn Morris +23 more
TL;DR: The broadly reactive HIV-1 neutralization observed in some subjects is mediated by antibodies targeting several conserved regions on the HIV- 1 envelope glycoprotein.
Journal ArticleDOI
Cell-cell transmission enables HIV-1 to evade inhibition by potent CD4bs directed antibodies
Irene A Abela,Livia Berlinger,Merle Schanz,Lucy Reynell,Huldrych F. Günthard,Peter Rusert,Alexandra Trkola +6 more
TL;DR: It is demonstrated that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action, providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo.
References
More filters
Journal ArticleDOI
Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
Peter D. Kwong,Richard T. Wyatt,James E. Robinson,Raymond W. Sweet,Joseph Sodroski,Wayne A. Hendrickson,Wayne A. Hendrickson +6 more
TL;DR: The structure reveals a cavity-laden CD4–gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion.
Journal ArticleDOI
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
Brandon F. Keele,Elena E. Giorgi,Elena E. Giorgi,Jesus F. Salazar-Gonzalez,Julie M. Decker,Kimmy T. Pham,Maria G. Salazar,Chuanxi Sun,Truman Grayson,Shuyi Wang,Hui Li,Xiping Wei,Chunlai Jiang,Jennifer L. Kirchherr,Feng Gao,Jeffery A. Anderson,Li Hua Ping,Ronald Swanstrom,Georgia D. Tomaras,William A. Blattner,Paul A. Goepfert,J. Michael Kilby,Michael S. Saag,Eric Delwart,Michael P. Busch,Myron S. Cohen,David C. Montefiori,Barton F. Haynes,Brian Gaschen,Gayathri Athreya,Ha Y. Lee,Natasha T. Wood,Cathal Seoighe,Alan S. Perelson,Tanmoy Bhattacharya,Tanmoy Bhattacharya,Bette T. Korber,Bette T. Korber,Beatrice H. Hahn,George M. Shaw +39 more
TL;DR: A mathematical model of random viral evolution and phylogenetic tree construction is developed and used to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection, suggesting a finite window of potential vulnerability of HIV- 1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.
Journal ArticleDOI
Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.
Laura M. Walker,Sanjay Phogat,Po-Ying Chan-Hui,Denise Wagner,Pham Phung,Julie L. Goss,Terri Wrin,Melissa Simek,Steven P. Fling,Jennifer L. Mitcham,Jennifer Lehrman,Frances Priddy,Ole A. Olsen,Steven Frey,Phillip W. Hammond,Protocol G. Principal Investigators,Stephen M. Kaminsky,Timothy J. Zamb,Matthew Moyle,Wayne C. Koff,Pascal Poignard,Dennis R. Burton,Dennis R. Burton +22 more
TL;DR: High-throughput screening has revealed two new broadly neutralizing antibodies from a clade A–infected donor in Africa, which exhibit great potency and are able to neutralize a wide range of viruses from many different clades.
Journal ArticleDOI
Design of a Novel Globular Protein Fold with Atomic-Level Accuracy
TL;DR: A general computational strategy that iterates between sequence design and structure prediction to design a 93-residue α/β protein called Top7 with a novel sequence and topology, found experimentally to be folded and extremely stable.
Journal ArticleDOI
The antigenic structure of the HIV gp120 envelope glycoprotein
Richard T. Wyatt,Peter D. Kwong,Elizabeth Desjardins,Raymond W. Sweet,James E. Robinson,Wayne A. Hendrickson,Joseph Sodroski +6 more
TL;DR: The spatial organization of conserved neutralization epitopes on gp120 is described, using epitope maps in conjunction with the X-ray crystal structure of a ternary complex that includes a gp120 core, CD4 and a neutralizing antibody.
Related Papers (5)
Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.
Laura M. Walker,Sanjay Phogat,Po-Ying Chan-Hui,Denise Wagner,Pham Phung,Julie L. Goss,Terri Wrin,Melissa Simek,Steven P. Fling,Jennifer L. Mitcham,Jennifer Lehrman,Frances Priddy,Ole A. Olsen,Steven Frey,Phillip W. Hammond,Protocol G. Principal Investigators,Stephen M. Kaminsky,Timothy J. Zamb,Matthew Moyle,Wayne C. Koff,Pascal Poignard,Dennis R. Burton,Dennis R. Burton +22 more
Broad neutralization coverage of HIV by multiple highly potent antibodies
Laura M. Walker,Michael Huber,Michael Huber,Katie J. Doores,Katie J. Doores,Emilia Falkowska,Emilia Falkowska,Robert Pejchal,Jean-Philippe Julien,Sheng-Kai Wang,Alejandra Ramos,Po-Ying Chan-Hui,Matthew Moyle,Jennifer L. Mitcham,Phillip W. Hammond,Ole A. Olsen,Pham Phung,Steven P. Fling,Chi-Huey Wong,Sanjay Phogat,Terri Wrin,Melissa Simek,Protocol G. Principal Investigators,Wayne C. Koff,Ian A. Wilson,Dennis R. Burton,Dennis R. Burton,Pascal Poignard,Pascal Poignard +28 more
Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding.
Johannes F. Scheid,Hugo Mouquet,Beatrix Ueberheide,Ron Diskin,Florian Klein,Thiago Y. Oliveira,John Pietzsch,John Pietzsch,David Fenyö,Alexander Abadir,Klara Velinzon,Arlene Hurley,Sunnie Myung,Farid Boulad,Pascal Poignard,Pascal Poignard,Dennis R. Burton,Dennis R. Burton,Florencia Pereyra,Florencia Pereyra,David D. Ho,Bruce D. Walker,Bruce D. Walker,Bruce D. Walker,Michael S. Seaman,Pamela J. Bjorkman,Pamela J. Bjorkman,Brian T. Chait,Michel C. Nussenzweig,Michel C. Nussenzweig +29 more
Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.
Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand
Supachai Rerks-Ngarm,Punnee Pitisuttithum,Sorachai Nitayaphan,Jaranit Kaewkungwal,Joseph Chiu,Robert Paris,Nakorn Premsri,Chawetsan Namwat,Mark de Souza,Elizabeth Adams,Michael Benenson,Sanjay Gurunathan,Jim Tartaglia,John G. McNeil,Donald P. Francis,Donald Stablein,Deborah L. Birx,Supamit Chunsuttiwat,Chirasak Khamboonruang,Prasert Thongcharoen,Merlin L. Robb,Nelson L. Michael,Prayura Kunasol,Jerome H. Kim +23 more