Thomas, P; Rees-Spear, C; Griffith, S; Muir, L; Touizer, E; Andrabi, R; Priest, R; ... McCoy, LE; + view all Thomas, P; Rees-Spear, C; Griffith, S; Muir, L; Touizer, E; Andrabi, R; Priest, R; Percival-Alwyn, J; Hayward, D; Buxton, A; Traylen, W; Chain, B; Wattam, T; Nandin, IS; McCoy, LE; - view fewer (2024) High affinity mAb infusion can enhance maximum affinity maturation during HIV Env immunization. iScience , 27 (4) , Article 109495. 10.1016/j.isci.2024.109495.

Preview

Text 1-s2.0-S2589004224007168-main.pdf - Published Version Download (5MB) | Preview

Abstract

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.

Download activity - last month

Export as CSVJSONXML

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item