5WHZ

PGDM1400-10E8v4 CODV Fab

Summary for 5WHZ

• Entry DOI: 10.2210/pdb5whz/pdb
• Descriptor: Anti-HIV CODV-Fab Light chain, Anti-HIV CODV-Fab Heavy chain (2 entities in total)
• Functional Keywords: cross-over dual variable immunoglobin, multifunctional biotherapeutic format, bispecific property, codv, hiv, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 80401.19

Authors

Lord, D.M.,Wei, R.R. (deposition date: 2017-07-18, release date: 2017-10-11, Last modification date: 2024-10-16)

Primary citation

Xu, L.,Pegu, A.,Rao, E.,Doria-Rose, N.,Beninga, J.,McKee, K.,Lord, D.M.,Wei, R.R.,Deng, G.,Louder, M.,Schmidt, S.D.,Mankoff, Z.,Wu, L.,Asokan, M.,Beil, C.,Lange, C.,Leuschner, W.D.,Kruip, J.,Sendak, R.,Do Kwon, Y.,Zhou, T.,Chen, X.,Bailer, R.T.,Wang, K.,Choe, M.,Tartaglia, L.J.,Barouch, D.H.,O'Dell, S.,Todd, J.P.,Burton, D.R.,Roederer, M.,Connors, M.,Koup, R.A.,Kwong, P.D.,Yang, Z.Y.,Mascola, J.R.,Nabel, G.J.
Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques.
Science, 358:85-90, 2017

PubMed Abstract: The development of an effective AIDS vaccine has been challenging because of viral genetic diversity and the difficulty of generating broadly neutralizing antibodies (bnAbs). We engineered trispecific antibodies (Abs) that 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. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates, in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and they may be applicable for treatment of diverse diseases, including infections, cancer, and autoimmunity.

PubMed: 28931639
DOI: 10.1126/science.aan8630

Experimental method

X-RAY DIFFRACTION (3.549 Å)