Enhancing Virus-Specific Immunity In Vivo by Combining Therapeutic Vaccination and PD-L1 Blockade in Chronic Hepadnaviral Infection

• DOI: 10.1371/journal.ppat.1003856
• Publication Date: 2014-01-02T21:51:09Z
• Authors: Jia Liu; Ejuan Zhang; Zhiyong Ma; Weimin Wu; Anna Kosinska; Xiaoyong Zhang; Inga Möller; Pia Seiz; Dieter Glebe; Baoju Wang; Dongliang Yang; Mengji Lu; Michael Roggendorf
• Keywords: Woodchuck hepatitis virus; Entecavir; Chronic infection

Hepatitis B virus (HBV) persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1). Improvement HBV-specific function has been obtained in vitro inhibiting PD-1/PD-ligand 1 (PD-L1) interaction. In this study, we examined whether vivo blockade PD-1 pathway enhances virus-specific immunity and leads to resolution chronic hepadnaviral infection woodchuck model. The was first cloned, characterized, its expression patterns on from woodchucks with acute or hepatitis (WHV) were investigated. Woodchucks chronically infected WHV received a combination therapy nucleoside analogue entecavir (ETV), therapeutic DNA vaccination PD-L1 antibody treatment. gain suppression replication evaluated. We could show correlated viral loads during infection. ETV treatment significantly decreased carriers. PD-1/PD-L1 cells, vaccination, potently enhanced cells. Moreover, suppressed replication, leading sustained immunological control infection, anti-WHs development complete clearance some woodchucks. Our results provide new approach improve which may be used design immunotherapeutic strategies patients.