Found 1 matching record:
Displaying record number 3570
Download this epitope
record as JSON.
Notes
Showing 2 of
2 notes.
-
PGT128-LM52: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PGT128-LM52: To improve the neutralization breadth and potency of the anti-CD4 antibody iMab, new bispecific mAbs were generated, consisting of iMab (or its variant, LM52) fused with anti-HIV mAbs. Three forms of VRC01-iMab were initially constructed using different orientations of the heavy and light chains, and different orientations of VRC01 and iMab. The best was chosen, and the same construction was applied to the other bispecifics. When the neutralization profiles of 3BNC60-iMab or PGT128-iMab were compared with the combination of their parental antibodies, the neutralization activity of the biAbs was consistently better. Increasing the length of the linker between the mAb and iMab from 20 to 25 or 47 amino acids was tested for VRC01-iMab and 3BNC60-iMab - the longer linker did not improve the neutralization potency. On a panel of 118 or 71 multi-clade pseudoviruses, VRC01-iMab, 3BNC60-iMab, NIH45-46-iMab, and VRC123-iMab neutralized 100% of tested viruses. Although PGT128-iMab did not neutralize 100% of tested viruses, the geometric mean of its IC50 values as lower (better) than that of the mAbs that achieved 100% breadth. At IC80, VRC01-iMab, 3BNC60-iMab, NIH45-46-iMab, VRC123-iMab, and VRC128-LM52 neutralized 99%, 97%, 100%, 97%, and 99% of tested pseudoviruses, respectively. The best neutralization profiles obtained were for VRC128-LM52 and VRC123-iMab, both of which could inhibit 100% of tested viruses with IC50 below 6 ng/ml. The potency of VRC128-LM52 was slighter better than the previously-published PG9-iMab.
Song2016
(antibody generation, neutralization, bispecific/trispecific, broad neutralizer)
References
Showing 2 of
2 references.
Isolation Paper
Song2016
Ruijiang Song, Craig Pace, Michael S. Seaman, Qing Fang, Ming Sun, Chasity D. Andrews, Amos Wu, Neal N. Padte, and David D. Ho. Distinct HIV-1 Neutralization Potency Profiles of Ibalizumab-Based Bispecific Antibodies. J. Acquir. Immune Defic. Syndr., 73(4):365-373, 1 Dec 2016. PubMed ID: 27792681.
Show all entries for this paper.
Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
Show all entries for this paper.
This is a legacy search page. It is deprecated, will
receive no more updates, and will eventually be removed. Please use
the new search pages.