Durable lymphocyte subset elimination upon a single dose of AAV-delivered depletion antibody dissects immune control of chronic viral infection.

Autor:	Kastner AL; Department of Biomedicine, University of Basel, 4009 Basel, Switzerland., Marx AF; Department of Biomedicine, University of Basel, 4009 Basel, Switzerland., Dimitrova M; Department of Biomedicine, University of Basel, 4009 Basel, Switzerland., Abreu-Mota T; Department of Biomedicine, University of Basel, 4009 Basel, Switzerland., Ertuna YI; Department of Biomedicine, University of Basel, 4009 Basel, Switzerland., Bonilla WV; Department of Biomedicine, University of Basel, 4009 Basel, Switzerland., Stauffer K; Department of Biomedicine, University of Basel, 4009 Basel, Switzerland., Künzli M; Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland., Wagner I; Department of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland., Kreutzfeldt M; Department of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospital, 1206 Geneva, Switzerland., Merkler D; Department of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospital, 1206 Geneva, Switzerland., Pinschewer DD; Department of Biomedicine, University of Basel, 4009 Basel, Switzerland. Electronic address: daniel.pinschewer@unibas.ch.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2024 Dec 17. Date of Electronic Publication: 2024 Dec 17.
DOI:	10.1016/j.immuni.2024.11.021
Abstrakt:	To interrogate the role of specific immune cells in infection, cancer, and autoimmunity, immunologists commonly use monoclonal depletion antibodies (depletion-mAbs) or genetically engineered mouse models (GEMMs). To generate a tool that combines specific advantages and avoids select drawbacks of the two methods, we engineered adeno-associated viral vectors expressing depletion mAbs (depletion-AAVs). Single-dose depletion-AAV administration durably eliminated lymphocyte subsets in mice and avoided accessory deficiencies of GEMMs, such as marginal zone defects in B cell-deficient animals. Depletion-AAVs can be used in animals of different genetic backgrounds, and multiple depletion-AAVs can readily be combined. Exploiting depletion-AAV technology, we showed that B cells were required for unimpaired CD4 + and CD8 + T cell responses to chronic lymphocytic choriomeningitis virus (LCMV) infection. Upon B cell depletion, CD8 + T cells failed to suppress viremia, and they only helped resolve chronic infection when antibodies dampened viral loads. Our study positions depletion-AAVs as a versatile tool for immunological research. Competing Interests: Declaration of interests D.D.P. is a founder, consultant, and shareholder of Hookipa Pharma Inc. commercializing arenavirus-based vector technology, and he as well as W.V.B. and D.M. are listed as inventors on corresponding patents. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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