EMD-41810
Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env Local Refinement
EMD-41810
Single-particle4.25 Å
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Map released: 03/01/2024
Last modified: 13/11/2024
Sample Organism:
Macaca mulatta,
Human immunodeficiency virus 1
Sample: The complex of vaccine elicited CD4 binding site neutralizing antibody DH1285 Fab with CH505M5chimer.6R.SOSIP.664v4.1 Env
Fitted models: 8u1d (Avg. Q-score: 0.359)
Deposition Authors: Thakur B
,
Stalls VD,
Acharya P
Sample: The complex of vaccine elicited CD4 binding site neutralizing antibody DH1285 Fab with CH505M5chimer.6R.SOSIP.664v4.1 Env
Fitted models: 8u1d (Avg. Q-score: 0.359)
Deposition Authors: Thakur B
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Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.
Saunders KO,
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 SM,
Santra S,
Weissman D,
Moody MA,
Cain DW,
Tam YK,
Lewis M,
Williams WB,
Wiehe K,
Montefiori DC,
Acharya P
,
Haynes BF
(2024) Cell , 187 , 79 - 94.e24
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(2024) Cell , 187 , 79 - 94.e24
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.
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.