OVA-Texo/4-1BBL helped restore exhausted OVA-specific CD8+ T cell function during Adenovirus induced chronic infection. (VAC12P.1115)

Abstract

Abstract CD8+ T cell functional exhaustion has been adequately studied during established persistent viral infections such as LCMV in mice models as well as HIV and hepatitis C virus (HCV) in human chronic infections. Recombinant Adenovirus infection has also been reported to cause CD8+ T cell dysfunction and deletion. In this study, we established an Adenovirus induced chronic infection in C57BL/6 mice, characteristic by a long persistence of high percentage of antigen-specific CD8+ T cells, with increased inhibitory markers expression (PD-L1, PD-1, LAG-3, CD43) and compromised effector functions. Exosome-targeted CD8+ T cell vaccine is constructed through ConA stimulated non-specific CD8+T cells uptaking OVA pulsed DC-derived exosome (EXO), acting as CD8+Tc antigen presenting cells (Th-APCs), and capable of stimulating DC- and CD4+T cell-independent OVA-specific CTL responses leading to long-term immunity. We demonstrated that OVA-Texo/4-1BBL vaccine is able to provoke a successful immune response in chronic infected mice, increasing OVA-specific CD8+ cell level massively by approximately 3-fold, the primed CTLs could differentiate into functional CD8+ memory T cells. OVA-Texo/4-1BBL also helped restore exhausted CD8+ T cell function in the absence of CD4+ T cells. A sufficient increase of IFN-r production CD8+ T cell was measured after OVA-Texo/4-1BBL immunization compared with mice without treatment.