Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41.
Michael B. Zwick,Aran F. Labrijn,Min Wang,Catherine Spenlehauer,Erica Ollmann Saphire,James M. Binley,John P. Moore,Gabriela Stiegler,Hermann Katinger,Dennis R. Burton,Paul W. H. I. Parren +10 more
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TLDR
The results suggest that a rather extensive region of gp41 close to the transmembrane domain is accessible to neutralizing Abs and could form a useful target for vaccine design.Abstract:
The identification and epitope mapping of broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies (Abs) is important for vaccine design, but, despite much effort, very few such Abs have been forthcoming. Only one broadly neutralizing anti-gp41 monoclonal Ab (MAb), 2F5, has been described. Here we report on two MAbs that recognize a region immediately C-terminal of the 2F5 epitope. Both MAbs were generated from HIV-1-seropositive donors, one (Z13) from an antibody phage display library, and one (4E10) as a hybridoma. Both MAbs recognize a predominantly linear and relatively conserved epitope, compete with each other for binding to synthetic peptide derived from gp41, and bind to HIV-1(MN) virions. By flow cytometry, these MAbs appear to bind relatively weakly to infected cells and this binding is not perturbed by pretreatment of the infected cells with soluble CD4. Despite the apparent linear nature of the epitopes of Z13 and 4E10, denaturation of recombinant envelope protein reduces the binding of these MAbs, suggesting some conformational requirements for full epitope expression. Most significantly, Z13 and 4E10 are able to neutralize selected primary isolates from diverse subtypes of HIV-1 (e.g., subtypes B, C, and E). The results suggest that a rather extensive region of gp41 close to the transmembrane domain is accessible to neutralizing Abs and could form a useful target for vaccine design.read more
Citations
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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.
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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
TL;DR: Anti-HIV broadly neutralizing antibodies with similar specificities and modes of binding were found in multiple HIV-infected individuals, and cloned 576 new HIV antibodies from four unrelated individuals to determine whether they are part of a larger group of related molecules.
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Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
Johannes F. Scheid,Hugo Mouquet,Niklas Feldhahn,Michael S. Seaman,Klara Velinzon,John Pietzsch,Rene G. Ott,Robert M. Anthony,Henry Zebroski,Arlene Hurley,Adhuna Phogat,Bimal K. Chakrabarti,Yuxing Li,Mark Connors,Florencia Pereyra,Bruce D. Walker,Hedda Wardemann,David D. Ho,Richard T. Wyatt,John R. Mascola,Jeffrey V. Ravetch,Michel C. Nussenzweig +21 more
TL;DR: The IgG memory B-cell compartment in the selected group of patients with broad serumneutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.
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TL;DR: Current approaches to overcome the problems faced in eliciting broadly neutralizing antibodies to human immunodeficiency virus could bring closer the goal of a successful AIDS vaccine.
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Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition
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