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Displaying record number 3278

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MAb ID	PG16-iMab (PG16-ibalizumab)
HXB2 Location	Env	Env Epitope Map
Author Location
Epitope
Ab Type	gp120 V2 // V2 glycan(V2g) // V2 apex, non-HIV: host CD4R
Neutralizing	P (tier 2) View neutralization details
Species (Isotype)	human
Patient	Donor 24
Immunogen
Keywords	antibody generation, bispecific/trispecific, chimeric antibody, immunotherapy, neutralization, review, subtype comparisons

Notes

Showing 4 of 4 notes.

PG16-iMab: A panel of bnAbs were studied to assess ongoing adaptation of the HIV-1 species to the humoral immunity of the human population. Resistance to neutralization is increasing over time, but concerns only the external glycoprotein gp120, not the MPER, suggesting a high selective pressure on gp120. Almost all the identified major neutralization epitopes of gp120 are affected by this antigenic drift, suggesting that gp120 as a whole has progressively evolved in less than 3 decades. Bouvin-Pley2014 (neutralization)
PG16-iMab: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibodies fused to iMab are mentioned as an example of engineering through combining mAbs to target host cellular receptors and thus restrict viral escape. Hua2016 (immunotherapy, review, bispecific/trispecific)
PG16-iMab: This study examined the neutralization of group N, O, and P primary isolates of HIV-1 by diverse antibodies. Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O isolates, 1 group N isolate, and the group P isolates were neutralized by PG9 and/or PG16 or PGT145 at low concentrations. None of the non-M primary isolates were neutralized by bNAbs targeting other regions, except 10E8, which weakly neutralized 2 group N isolates, and 35O22 which neutralized 1 group O isolate. Bispecific bNAbs (PG9-iMab and PG16-iMab) very efficiently neutralized all non-M isolates with IC₅₀ below 1 ug/mL, except for 2 group O strains. Bispecific bNAb PG16-iMab was able to neutralize all 16 tested non-M primary isolates at an IC₅₀< 10µg/ml, 15 of them under 1 µg/ml (see Table 2 for values). Morgand2015 (neutralization, subtype comparisons, bispecific/trispecific)
PG16-iMab: Ibalizumab (iMab), an anti-CD4 antibody, was used as a scaffold to attach the antigen binding domain of either PG9 or PG16 to create bispecific antibodies. PG9-iMab and PG16-iMab showed remarkable breadth and potency in neutralizing 100% of 118 diverse HIV strains, including strains resistant to both of the parental antibodies. 72% of viruses were neutralized at an IC₅₀ of 10ng/ml or less. Pace2013a (antibody generation, neutralization, bispecific/trispecific, chimeric antibody)

References

Showing 4 of 4 references.

Isolation Paper
Pace2013a Craig S. Pace, Ruijiang Song, Christina Ochsenbauer, Chasity D. Andrews, David Franco, Jian Yu, Deena A. Oren, Michael S. Seaman, and David D. Ho. Bispecific Antibodies Directed to CD4 Domain 2 and HIV Envelope Exhibit Exceptional Breadth and Picomolar Potency against HIV-1. Proc. Natl. Acad. Sci. U.S.A., 110(33):13540-13545, 13 Aug 2013. PubMed ID: 23878231. Show all entries for this paper.

Bouvin-Pley2014 M. Bouvin-Pley, M. Morgand, L. Meyer, C. Goujard, A. Moreau, H. Mouquet, M. Nussenzweig, C. Pace, D. Ho, P. J. Bjorkman, D. Baty, P. Chames, M. Pancera, P. D. Kwong, P. Poignard, F. Barin, and M. Braibant. Drift of the HIV-1 Envelope Glycoprotein gp120 Toward Increased Neutralization Resistance over the Course of the Epidemic: A Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J. Virol., 88(23):13910-13917, Dec 2014. PubMed ID: 25231299. Show all entries for this paper.

Hua2016 Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912. Show all entries for this paper.

Morgand2015 Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, François Simon, Craig S. Pace, Marie Pancera, David D. Ho, Pascal Poignard, Pamela J. Bjorkman, Hugo Mouquet, Michel C. Nussenzweig, Peter D. Kwong, Daniel Baty, Patrick Chames, Martine Braibant, and Francis Barin. A V1V2 Neutralizing Epitope Is Conserved in Divergent Non-M Groups of HIV-1. J. Acquir. Immune Defic. Syndr., 21 Sep 2015. PubMed ID: 26413851. Show all entries for this paper.