8U1D

Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env Local Refinement

Summary for 8U1D

• Entry DOI: 10.2210/pdb8u1d/pdb
• EMDB information: 41810
• Descriptor: Envelope glycoprotein gp120, DH1285 Heavy Chain, DH1285 Light Chain, ... (4 entities in total)
• Functional Keywords: hiv-1 vaccine induced neutralizing antibody, cd4 binding site antibody, gp120, dh1285, igg, rhesus macaques, ch505m5chimer.6r.sosip.664v4.1 env, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 124527.56

Authors

Thakur, B.,Stalls, V.D.,Acharya, P. (deposition date: 2023-08-31, release date: 2024-01-03, Last modification date: 2024-11-13)

Primary citation

Saunders, K.O.,Counts, J.,Thakur, B.,Stalls, V.,Edwards, R.,Manne, K.,Lu, X.,Mansouri, K.,Chen, Y.,Parks, R.,Barr, M.,Sutherland, L.,Bal, J.,Havill, N.,Chen, H.,Machiele, E.,Jamieson, N.,Hora, B.,Kopp, M.,Janowska, K.,Anasti, K.,Jiang, C.,Van Itallie, E.,Venkatayogi, S.,Eaton, A.,Henderson, R.,Barbosa, C.,Alam, S.M.,Santra, S.,Weissman, D.,Moody, M.A.,Cain, D.W.,Tam, Y.K.,Lewis, M.,Williams, W.B.,Wiehe, K.,Montefiori, D.C.,Acharya, P.,Haynes, B.F.
Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.
Cell, 187:79-94.e24, 2024

PubMed Abstract: The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.

PubMed: 38181743
DOI: 10.1016/j.cell.2023.12.002

Experimental method

ELECTRON MICROSCOPY (4.25 Å)