Skeletal muscle is an antigen reservoir in integrase-defective lentiviral vector-induced long-term immunity

Abstract We previously developed Integrase-Defective Lentiviral Vectors (IDLVs) as antigen delivery system for inducing strong and prolonged immunity in animal models. Here, we examined the association between persistence of antigen expression and durability of immune response. Following a single intramuscular (IM) or subcutaneous (SC) injection of IDLV delivering GFP in mice, we evaluated antigen expression and inflammation at the site of injection and persistence of antigen-specific T cells at early and late time points. Durable antigen expression was detected up to 90 days only post IM immunization. Mononuclear inflammation was evident soon after IDLV-injection in both IM and SC immunized mice, but remained detectable up to 30 days post injection only in IM immunized mice. Similarly, GFP-specific T cells were more persistent in the IM immunized mice. Interestingly, GFP+ muscle fibers were co-expressing MHC-I, suggesting that muscle cells are competent for presenting antigens to T cells in vivo. In in vitro experiments, we demonstrated that while both primary myoblasts and myocytes present the antigen to GFP-specific T cells through MHC-I, myoblasts are more resistant to Fas-dependent CTL killing activity. Overall these data indicate that muscle cells may serve as an antigen reservoir that contributes to the long-term immunity induced by IDLV vaccination.