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

Autor:	Thomas P; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK.; Biopharmaceutical Molecular Discovery Group, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK., Rees-Spear C; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Griffith S; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Muir L; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Touizer E; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK., Andrabi R; Department of Medicine, University of Pennsylvania, Philadelphia 19104, PA, USA., Priest R; Biopharmaceutical Molecular Discovery Group, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK., Percival-Alwyn J; Biopharmaceutical Molecular Discovery Group, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK., Hayward D; Biopharmaceutical Molecular Discovery Group, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK., Buxton A; In vivo Sciences and Delivery, GSK, Park Road, Ware SG12 0DP, UK., Traylen W; In vivo Sciences and Delivery, GSK, Park Road, Ware SG12 0DP, UK., Chain B; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK.; Department of Computer Science, University College London, London WC1E 6EA, UK., Wattam T; Biopharmaceutical Molecular Discovery Group, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK., Nandin IS; Immunology Research Unit, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK., McCoy LE; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Mar 11; Vol. 27 (4), pp. 109495. Date of Electronic Publication: 2024 Mar 11 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.109495
Abstrakt:	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. Competing Interests: R.P., J.P.A., D.H., A.B., W.T., T.W., and I.S.N. are employees and shareholders in GSK plc. No other authors have competing interests to declare. (© 2024 The Authors.)
Databáze:	MEDLINE
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