EMD-40982
BG505 Boost2 SOSIP.664 in complex with NHP polyclonal antibody N289
EMD-40982
Single-particle3.8 Å
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Map released: 12/06/2024
Last modified: 16/10/2024
Sample Organism:
Human immunodeficiency virus 1,
Macaca mulatta
Sample: BG505 Boost 2 in complex with NHP Polyclonal Antibody N289
Fitted models: 8t2f (Avg. Q-score: 0.424)
Deposition Authors: Pratap PP
,
Antansijevic A,
Ozorowski G
,
Ward AB
Sample: BG505 Boost 2 in complex with NHP Polyclonal Antibody N289
Fitted models: 8t2f (Avg. Q-score: 0.424)
Deposition Authors: Pratap PP
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Priming antibody responses to the fusion peptide in rhesus macaques.
Cottrell CA
,
Pratap PP
,
Cirelli KM,
Carnathan DG,
Enemuo CA,
Antanasijevic A
,
Ozorowski G
,
Sewall LM,
Gao H
,
Allen JD
,
Nogal B,
Silva M,
Bhiman J,
Pauthner M,
Irvine DJ
,
Montefiori D,
Crispin M
,
Burton DR
,
Silvestri G,
Crotty S
,
Ward AB
(2024) NPJ Vaccines , 9 , 126 - 126
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(2024) NPJ Vaccines , 9 , 126 - 126
Abstract:
Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.
Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.