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Displaying record number 3956

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MAb ID	N6/PGDM1400-10E8v4 (N6-LS/PGDM1400-10E8v4)
HXB2 Location	gp160	gp160 Epitope Map
Author Location
Epitope
Ab Type	gp120 CD4BS, gp120 V2 // V2 glycan(V2g) // V2 apex, gp41 MPER (membrane proximal external region)
Neutralizing	P View neutralization details
Species (Isotype)	human
Patient	Donor 84, Donor N152, Z258
Immunogen	HIV-1 infection, engineered
Keywords	antibody generation, binding affinity, bispecific/trispecific, neutralization

Notes

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Database note: The construction of this trispecific mAb included the incorporation of the "LS" mutation, which confers increased binding to FcRn and increases the half-life of the Ab. Thus we include the synonym N6-LS/PGDM1400-10E8v4 for this mAb.
N6/PGDM1400-10E8v4: Combinations of single and bispecific Abs (PGDM1400, CD4bs, 10E8, 10E8v4, N6, VRC01, PGT121) were assessed for binding and neutralization. Trispecific Abs were engineered to allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site. The trispecific antibodies were highly potent and broadly neutralized ˜99% of a large multiclade panel of HIV and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates. When analyzed against a panel of 208 viruses and compared to the parental antibodies alone, the highest neutralization potency and breadth were observed with N6/PGDM1400-10E8v4, with only 1 of the 208 viruses showing neutralization resistance and a median IC₅₀ of less than 0.02 mg/ml and 0.5% viruses resistant to neutralization at an IC₅₀ of >50 µg/ml. Xu2017 (antibody generation, neutralization, binding affinity, bispecific/trispecific)

References

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Isolation Paper
Xu2017 Ling Xu, Amarendra Pegu, Ercole Rao, Nicole Doria-Rose, Jochen Beninga, Krisha McKee, Dana M. Lord, Ronnie R. Wei, Gejing Deng, Mark Louder, Stephen D. Schmidt, Zachary Mankoff, Lan Wu, Mangaiarkarasi Asokan, Christian Beil, Christian Lange, Wulf Dirk Leuschner, Jochen Kruip, Rebecca Sendak, Young Do Kwon, Tongqing Zhou, Xuejun Chen, Robert T. Bailer, Keyun Wang, Misook Choe, Lawrence J. Tartaglia, Dan H. Barouch, Sijy O'Dell, John-Paul Todd, Dennis R. Burton, Mario Roederer, Mark Connors, Richard A. Koup, Peter D. Kwong, Zhi-Yong Yang, John R. Mascola, and Gary J. Nabel. Trispecific Broadly Neutralizing HIV Antibodies Mediate Potent SHIV Protection in Macaques. Science, 358(6359):85-90, 6 Oct 2017. PubMed ID: 28931639. Show all entries for this paper.