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Displaying record number 2183
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MAb ID |
1-74 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Epitope |
|
Ab Type |
|
Neutralizing |
|
Species
(Isotype)
|
human(IgG) |
Patient |
Patient 1 |
Immunogen |
HIV-1 infection |
Keywords |
antibody binding site, antibody generation, antibody polyreactivity, antibody sequence, autologous responses, binding affinity, chimeric antibody, elite controllers and/or long-term non-progressors, escape, kinetics, neutralization, optimal epitope, polyclonal antibodies, variant cross-reactivity |
Notes
Showing 5 of
5 notes.
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1-74: bNAbs were found to have potent activating but not inhibitory FcγR-mediated effector function that can confer protection by blocking viral entry or suppressing viremia. bNAb activity is augmented with engineered Fc domains when assessed in in vivo models of HIV-1 entry or in therapeutic models using HIV-1-infected humanized mice. Enhanced FcγR engagement is not restricted by epitope specificity or neutralization potency as chimeras composed of poorly neutralizing human anti-CD4bs 1-74 Fab and mouse Fc had improved or reduced in vivo activity depending on the Fc used.
Bournazos2014
(neutralization, chimeric antibody)
-
1-74: Neutralizing antibody response was studied in elite controller. Subject VC10042 is an African American male, infected with clade B for 2 decades (since 1984) without any signs of disease and no antiretroviral treatment. The neutralizing activity of autologous CD4bs NAbs was very similar to that of NIH45-46W, but very different from other anti-CD4bs MAbs tested. The viral autologous variants that were resistant to neutralization by autologous and most bnMAbs tested had an extremely rare R272/N368 combination. This mutation was shown in the study to impart a fitness cost to the virus.
Sather2012
(autologous responses, elite controllers and/or long-term non-progressors, neutralization, escape, polyclonal antibodies)
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1-74: 134 unique anti-gp140 and 52 control non-gp140 reactive antibodies were studied for polyreactivity and its effect on binding affinity and neutralization. 75% of antibodies were polyreactive. 1-74 is sensitive to neutralization and binds to ssDNA, dsDNA, LPS (lipopolysaccharide), Insulin, ANA (antinuclear antibody) and CL (cardiolipin).
Mouquet2010
(neutralization, binding affinity, antibody polyreactivity)
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1-74: Substitutions in the CD4bs (E370A and/or D368A) or in close proximity to the CD4bs (N276A, R480A and Y384A) reduced binding of b12 but had no effect on binding activity of 1-74, indicating that binding characteristics of the anti-CD4bs Ab and anti-core Abs are distinct. Three mutations, D747A, M475A and R476A, had no effect on b12 binding but reduced binding of anti-core Abs, but not that of 1-74 MAb. These three residues were shown to be required for optimal viral infectivity. These results indicate that anti-core Abs recognize a conformational epitope including the α5 helix at the outer-domain-inner-domain junction of gp120. The epitope was highly conserved across different HIV-1 isolates.
Pietzsch2010a
(antibody binding site, optimal epitope, variant cross-reactivity, binding affinity)
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1-74: This Ab was cloned from HIV envelope-binding memory B cells from a patient with broadly neutralizing Abs in serum, and was reactive to gp120 core, recognizing epitope in the vicinity of the CD4bs and the CD4i site. 1-74 was shown to have high affinity for gp140, and competed with b12 for binding to gp140. 1-74 was able to neutralize 3/5 Tier 1 viruses and 1/5 Tier 2 viruses. 1-74 did not show broad serum-neutralizing activity. In total, 433 Abs were isolated from 6 patients, with neutralizing activity directed against several epitopes on gp120. Tier-2 neutralization was observed only with mixtures of MAbs, but only at high concentrations.
Scheid2009
(antibody generation, neutralization, kinetics, binding affinity, antibody sequence)
References
Showing 5 of
5 references.
Isolation Paper
Scheid2009
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 Chakrabarti, Yuxing Li, Mark Connors, Florencia Pereyra, Bruce D. Walker, Hedda Wardemann, David Ho, Richard T. Wyatt, John R. Mascola, Jeffrey V. Ravetch, and Michel C. Nussenzweig. Broad Diversity of Neutralizing Antibodies Isolated from Memory B Cells in HIV-Infected Individuals. Nature, 458(7238):636-640, 2 Apr 2009. PubMed ID: 19287373.
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Bournazos2014
Stylianos Bournazos, Florian Klein, John Pietzsch, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity. Cell, 158(6):1243-1253, 11 Sep 2014. PubMed ID: 25215485.
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Mouquet2010
Hugo Mouquet, Johannes F. Scheid, Markus J. Zoller, Michelle Krogsgaard, Rene G. Ott, Shetha Shukair, Maxim N. Artyomov, John Pietzsch, Mark Connors, Florencia Pereyra, Bruce D. Walker, David D. Ho, Patrick C. Wilson, Michael S. Seaman, Herman N. Eisen, Arup K. Chakraborty, Thomas J. Hope, Jeffrey V. Ravetch, Hedda Wardemann, and Michel C. Nussenzweig. Polyreactivity Increases the Apparent Affinity of Anti-HIV Antibodies by Heteroligation. Nature, 467(7315):591-595, 30 Sep 2010. PubMed ID: 20882016.
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Pietzsch2010a
John Pietzsch, Johannes F. Scheid, Hugo Mouquet, Florian Klein, Michael S. Seaman, Mila Jankovic, Davide Corti, Antonio Lanzavecchia, and Michel C. Nussenzweig. Human Anti-HIV-Neutralizing Antibodies Frequently Target a Conserved Epitope Essential for Viral Fitness. J. Exp. Med., 207(9):1995-2002, 30 Aug 2010. PubMed ID: 20679402.
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Sather2012
D. Noah Sather, Sara Carbonetti, Jenny Kehayia, Zane Kraft, Iliyana Mikell, Johannes F. Scheid, Florian Klein, and Leonidas Stamatatos. Broadly Neutralizing Antibodies Developed by an HIV-Positive Elite Neutralizer Exact a Replication Fitness Cost on the Contemporaneous Virus. J. Virol., 86(23):12676-12685, Dec 2012. PubMed ID: 22973035.
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