Journal ArticleDOI
Characterizing anti-HIV monoclonal antibodies and immune sera by defining the mechanism of neutralization.
Emma T. Crooks,Penny L. Moore,Douglas D. Richman,James E. Robinson,Jeffrey A. Crooks,Michael Franti,Norbert Schülke,James M. Binley +7 more
TLDR
Using JR-FL as a prototype primary pseudovirus and several neutralization formats designed to elucidate the timing of anti-HIV monoclonal antibodies, it is concluded that these methods, together with other mapping approaches, may provide a better understanding of neutralization that could be useful in vaccine research.Abstract:
Understanding the nature of neutralization may provide information for crafting improvements in HIV vaccines. Using JR-FL as a prototype primary pseudovirus, we first investigated anti-HIV monoclonal antibodies (mAbs) in several neutralization formats designed to elucidate the timing of neutralization. MAb b12 was most effective before receptor binding, 2G12 neutralized effectively even after CD4 binding, and X5 and a V3 loop mAb (LE311) were inactive in a standard format but were induced by sCD4. Consistent with this latter finding, native PAGE indicated that X5 and V3 mAb binding to Envelope trimers was dependent on sCD4 binding. In contrast, 2F5 and 4E10 were active even post-CD4/CCR5 engagement. We next analyzed the neutralization mechanism of a panel of HIV+ donor plasmas of various potencies. All mediated high levels of post-CD4 neutralization that was not associated with activity in the standard format. None, however, neutralized effectively in the post-CD4/CCR5 format, suggesting that 2F5/4E10-like Abs were absent or at low concentrations. Finally, we analyzed a non-neutralizing plasma spiked with mAbs b12, 2G12 or 2F5, which resulted in increases in neutralization titers consistent with the activities of the mAbs. We conclude that these methods, together with other mapping approaches, may provide a better understanding of neutralization that could be useful in vaccine research.read more
Citations
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Journal ArticleDOI
Broad and potent HIV-1 neutralization by a human antibody that binds the gp41–gp120 interface
Jinghe Huang,Byong H. Kang,Marie Pancera,Jeong Hyun Lee,Tommy Tong,Yu Feng,Hiromi Imamichi,Ivelin S. Georgiev,Gwo-Yu Chuang,Aliaksandr Druz,Nicole A. Doria-Rose,Leo B. Laub,Kwinten Sliepen,Marit J. van Gils,Alba Torrents de la Peña,Ronald Derking,Per Johan Klasse,Stephen A. Migueles,Robert T. Bailer,Munir Alam,Pavel Pugach,Barton F. Haynes,Richard T. Wyatt,Rogier W. Sanders,James M. Binley,Andrew B. Ward,John R. Mascola,Peter D. Kwong,Mark Connors +28 more
TL;DR: A broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope, which represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection.
Journal ArticleDOI
Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer.
TL;DR: Cryo–electron microscopy is used to solve the structure of a trimeric Env protein of HIV-1, missing only its cytoplasmic tail, in complex with broadly neutralizing antibodies, providing new insights into the wild-type Env structure.
Journal ArticleDOI
Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C
James M. Binley,Elizabeth A. Lybarger,Emma T. Crooks,Michael S. Seaman,Elin S. Gray,Katie L. Davis,Julie M. Decker,Diane Wycuff,Linda Harris,Natalie Hawkins,Blake Wood,Cory Nathe,Douglas D. Richman,Georgia D. Tomaras,Frederic Bibollet-Ruche,James E. Robinson,Lynn Morris,George M. Shaw,David C. Montefiori,John R. Mascola +19 more
TL;DR: Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs.
Journal ArticleDOI
Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials
David C. Montefiori,Chitraporn Karnasuta,Ying Huang,Hasan Ahmed,Peter B. Gilbert,Mark de Souza,Robert McLinden,Sodsai Tovanabutra,Agnes Laurence-Chenine,Eric Sanders-Buell,M. Anthony Moody,Mattia Bonsignori,Christina Ochsenbauer,John C. Kappes,Haili Tang,Kelli Greene,Hongmei Gao,Celia C. LaBranche,Charla Andrews,Victoria R. Polonis,Supachai Rerks-Ngarm,Punnee Pitisuttithum,Sorachai Nitayaphan,Jaranit Kaewkungwal,Steve Self,Phillip W. Berman,Donald P. Francis,Faruk Sinangil,Carter Lee,Jim Tartaglia,Merlin L. Robb,Barton F. Haynes,Nelson L. Michael,Jerome H. Kim +33 more
TL;DR: The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies.
Journal ArticleDOI
The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design
TL;DR: The identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target.
References
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Journal ArticleDOI
Rapid evolution of the neutralizing antibody response to HIV type 1 infection
TL;DR: Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations.
Journal ArticleDOI
CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5
Lijun Wu,Norma P. Gerard,Richard T. Wyatt,Hyeryun Choe,Cristina Parolin,Nancy Ruffing,Alessândra Borsetti,Angelo A. Cardoso,Elizabeth Desjardin,Walter Newman,Craig Gerard,Joseph Sodroski +11 more
TL;DR: It is suggested that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry.
Journal ArticleDOI
Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody
Dennis R. Burton,Jayashree Pyati,Raju Koduri,Stephen J. Sharp,George B. Thornton,Paul W. H. I. Parren,Lynette S. W. Sawyer,R. Michael Hendry,N Dunlop,Peter L. Nara,Michael Lamacchia,Eileen Garratty,E. Richard Stiehm,Yvonne J. Bryson,Yunzhen Cao,John P. Moore,David D. Ho,Carlos F. Barbas +17 more
TL;DR: A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization, implying the conservation of a structural feature on gp120, which could be important in vaccine design.
Journal ArticleDOI
Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies
Ming Li,Feng Gao,John R. Mascola,Leonidas Stamatatos,Victoria R. Polonis,Marguerite Koutsoukos,Gerald Voss,Paul A. Goepfert,Peter B. Gilbert,Kelli Greene,Miroslawa Bilska,Denise Kothe,Jesus F. Salazar-Gonzalez,Xiping Wei,Julie M. Decker,Beatrice H. Hahn,David C. Montefiori +16 more
TL;DR: There is an urgent need to establish standard panels of HIV-1 reference strains for wide distribution and a lack of uniformity in target strains used by different investigators to assess cross-neutralization has made the comparison of vaccine-induced antibody responses difficult.
Journal ArticleDOI
CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5.
Alexandra Trkola,Tatjana Dragic,James Arthos,James M. Binley,William C. Olson,Graham P. Allaway,Cecilia Cheng-Mayer,James E. Robinson,Paul J. Maddon,John P. Moore +9 more
TL;DR: CD4 binding, although not absolutely necessary for the gp120–CCR-5 interaction, greatly increases its efficiency, and interference with HIV-1 binding to one or both of its receptors (CD4 and CCR-5) may be an important mechanism of virus neutralization.
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