Regulatory T cells and TLR9 activation shape antibody formation to a secreted transgene product in AAV muscle gene transfer.

ABSTRACT: Adeno-associated viral (AAV) gene delivery to skeletal muscle is being explored for systemic delivery of therapeutic proteins. To better understand the signals that govern antibody formation against secreted transgene products in this approach, we administered an intramuscular dose of AAV1 vector expressing human coagulation factor IX (hFIX), which does not cause antibody formation against hFIX in C57BL/6 mice. Interestingly, co-administration of a TLR9 agonist (CpG-deoxyoligonucleotide, ODN) but not of lipopolysaccharide, caused a transient anti-hFIX response. ODN activated monocyte-derived dendritic cells and enhanced T follicular helper cell responses. While depletion of regulatory T cells (Tregs) also caused an antibody response, TLR9 activation combined with Treg depletion instead res

SUBMITTER: Herzog RW 

PROVIDER: S-EPMC5794662 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature