EMD-7885
BG505 MD64 N332-GT5 SOSIP trimer in complex with BG18-like precursor HMP42 fragment antigen binding and base-binding RM20A3 fragment antigen binding
EMD-7885
Single-particle3.43 Å
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Map released: 06/11/2019
Last modified: 18/12/2019
Sample Organism:
Homo sapiens,
Macaca mulatta,
Human immunodeficiency virus 1
Sample: BG505 MD64 N332-GT5 SOSIP trimer in complex with BG18-like precursor HMP42 fragment antigen binding and base-binding RM20A3 fragment antigen binding
Deposition Authors: Torres JL, Ozorowski G, Steichen JM, Schief WR, Ward AB
Sample: BG505 MD64 N332-GT5 SOSIP trimer in complex with BG18-like precursor HMP42 fragment antigen binding and base-binding RM20A3 fragment antigen binding
Deposition Authors: Torres JL, Ozorowski G, Steichen JM, Schief WR, Ward AB
A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses.
Steichen JM
,
Lin YC
,
Havenar-Daughton C
,
Pecetta S
,
Ozorowski G,
Willis JR
,
Toy L
,
Sok D
,
Liguori A
,
Kratochvil S
,
Torres JL
,
Kalyuzhniy O
,
Melzi E
,
Kulp DW
,
Raemisch S
,
Hu X
,
Bernard SM,
Georgeson E,
Phelps N
,
Adachi Y
,
Kubitz M,
Landais E
,
Umotoy J
,
Robinson A
,
Briney B
,
Wilson IA
,
Burton DR
,
Ward AB
,
Crotty S
,
Batista FD
,
Schief WR
(2019) Science , 366
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(2019) Science , 366
Abstract:
Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.
Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.