Bone-marrow derived Dendritic cells can effectively be pulsed by HBVsvp and induce specific immune reactions in Balb/c mice

Introduction: Chronic Hepatitis B Virus (HBV) infection is a leading cause of liver fibrosis, cirrhosis and development of hepatocellular carcinoma. While virus replication can effectively be controlled by potent new nucleoside and nucleotide analogas, HBs seroconversion, as marker of viral eradication, is achieved very rarely. Therapeutic cell based approaches, like interferon therapy, have a better chance to lead to seroconversion. Dendritic cells (DCs) are key players in the cellular immune response and therefore have a high potential to control or eradicate viral infections. They have been shown to play an important role in controlling HBV infection.

Aim of the study: In this study, the potentiality of ex vivo activated DCs in inducing specific immune responses against HBV was examined. Therefore bone marrow derived DCs of Balb/c mice were, after a course of 8 day maturation with GMCS-F and IL-4, pulsed with HBV subviral particles (HBVsvp). HBVsvp are derived from the HepG2.2.15 cell line, producing subviral particles consisting of the HBc and HBs proteins, due to integrated HBV DNA. Thus, the whole „viral surface“ is presented to DCs to induce immune reaction.

Results: In vitro pulsation with HBVsvp led to a good activation of bone marrow derived DCs, shown by FACS analysis for MHCII, CD86 and CCR7. Immunization of Balb/c mice via sub cutaneous injection of such activated DCs, induced HBV specific immune reactions which were measured by ELISA and Elispot analysis.

Conclusion: Vaccination with ex vivo activated DCs may be a promising tool for therapeutic or prophylactic approaches against the Hepatitis B virus.

Dendritic cells - HBV - Hepatitis B - subviral particle