Priming antibody responses to the fusion peptide in rhesus macaques.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
12 Jul 2024
12 Jul 2024
Historique:
received:
20
06
2023
accepted:
27
06
2024
medline:
13
7
2024
pubmed:
13
7
2024
entrez:
12
7
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38997302
doi: 10.1038/s41541-024-00918-9
pii: 10.1038/s41541-024-00918-9
doi:
Types de publication
Journal Article
Langues
eng
Pagination
126Subventions
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : AI100663
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : AI144462
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : Al131873
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : AI048240
Organisme : Bill & Melinda Gates Foundation
ID : INV-007368
Pays : United States
Informations de copyright
© 2024. The Author(s).
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