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High affinity mAb infusion can enhance maximum affinity maturation during HIV Env immunization

Authors :
Peter Thomas
Chloe Rees-Spear
Sarah Griffith
Luke Muir
Emma Touizer
Raiees Andrabi
Richard Priest
Jennifer Percival-Alwyn
Darryl Hayward
Amanda Buxton
William Traylen
Benny Chain
Trevor Wattam
Irene Sanjuan Nandin
Laura E. McCoy
Source :
iScience, Vol 27, Iss 4, Pp 109495- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: Antigen-specific antibody infusion is known to enhance or suppress germinal center (GC) responses depending on the affinity of the infusion. We hypothesized that infusing monoclonal antibodies (mAbs) of escalating affinity during an immunization regimen may progressively escalate selection pressure on competing B cells, increasing their affinity. To test this, we immunized mice with HIV envelope gp120 and infused CD4 binding-site (CD4bs)-specific mAbs. While mAb infusion reduced somatic hypermutation (SHM) and affinity in most CD4bs-specific B cells, a sub-population was identified with greater SHM and affinity than control. High-throughput sequencing of plasma cells revealed that CD4bs-specific plasma cells possessed elevated SHM after mAb infusion, with phylogenetic tree topology that suggested more rapid differentiation. We therefore conclude, in accordance with other studies, that high-affinity mAb infusion primarily suppresses recruitment of most competing B cells but can increase and expedite affinity maturation of certain epitope-specific B cells.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
4
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.0b1bcca32ac54979a20f34a6710b4940
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2024.109495