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

Abstract

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 engineer adeno-associated viral vectors expressing depletion-mAbs (depletion-AAVs). Single-dose depletion-AAV administration permanently eliminates lymphocyte subsets in mice while avoiding accessory deficiencies of GEMMs such as marginal zone defects in B cell-deficient animals. Depletion-AAVs can be used irrespective of the animals genetic background, and multiple depletion-AAVs can readily be combined. Exploiting depletion-AAV technology, we show that B cells are required for unimpaired CD4 and CD8 T cell responses to chronic viral infection. Importantly, CD8 T cells fail to suppress viremia when B cells are depleted, and they only help resolving chronic infection if antibodies suppress viral loads. Our study positions depletion-AAVs as a versatile tool for immunological research.