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

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

doi:10.1016/j.isci.2024.109495

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

iScience. 2024 Mar 11;27(4):109495. doi: 10.1016/j.isci.2024.109495. eCollection 2024 Apr 19.

Authors

Peter Thomas^{1

2}, Chloe Rees-Spear¹, Sarah Griffith¹, Luke Muir¹, Emma Touizer¹, Raiees Andrabi³, Richard Priest², Jennifer Percival-Alwyn², Darryl Hayward², Amanda Buxton⁴, William Traylen⁴, Benny Chain^{1

5}, Trevor Wattam², Irene Sanjuan Nandin⁶, Laura E McCoy¹

Affiliations

¹ Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
² Biopharmaceutical Molecular Discovery Group, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK.
³ Department of Medicine, University of Pennsylvania, Philadelphia 19104, PA, USA.
⁴ In vivo Sciences and Delivery, GSK, Park Road, Ware SG12 0DP, UK.
⁵ Department of Computer Science, University College London, London WC1E 6EA, UK.
⁶ Immunology Research Unit, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK.

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.

Keywords: Immune response; Immunology; Virology.