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Displaying record number 3167

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MAb ID	45-46m25 (NIH45-46^{G54W,W47I(HC)S28Y(LC)})
HXB2 Location	Env	Env Epitope Map
Author Location
Epitope
Subtype	B
Ab Type	gp120 CD4BS
Neutralizing	P View neutralization details
Species (Isotype)	human(IgG)
Patient	NIH45
Immunogen	HIV-1 infection
Keywords	antibody generation, immunotherapy, neutralization, review, structure, subtype comparisons

Notes

Showing 3 of 3 notes.

45-46m25: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody 45-46m25 is an example of engineering through rational mutations; its neutralization is improved by avoiding steric clashes between the antibody and viral escape variants. Hua2016 (immunotherapy, review)
45-46m25: 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. Anti-CD4bs bNAb 45-46m25 was able to neutralize only 1/16 tested non-M primary isolates at an IC₅₀< 1 µg/ml, RBF208,M/O at 0.36 µg/ml. Morgand2015 (neutralization, subtype comparisons)
45-46m25: To increase the breadth of MAb NIH45-46^G54W, mutations were made in its light chain (S28Y) and heavy chain (W47I), creating MAb 45-46m25 (NIH45-46^{G54W,W47V(HC)S28Y(LC)}). 45-46m25 neutralized 6 YU-2 HIV-1 mutant strains, with 4/6 of them demonstrating IC₅₀ of less than 0.005 µg/ml. Diskin2013 (antibody generation, structure)

References

Showing 3 of 3 references.

Isolation Paper
Diskin2013 Ron Diskin, Florian Klein, Joshua A. Horwitz, Ariel Halper-Stromberg, D. Noah Sather, Paola M. Marcovecchio, Terri Lee, Anthony P. West, Jr., Han Gao, Michael S. Seaman, Leonidas Stamatatos, Michel C. Nussenzweig, and Pamela J. Bjorkman. Restricting HIV-1 Pathways for Escape Using Rationally Designed Anti-HIV-1 Antibodies. J. Exp. Med., 210(6):1235-1249, 3 Jun 2013. PubMed ID: 23712429. 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.