Analysis of immunological mechanisms exerted by HBsAg-HBIG therapeutic vaccine combined with Adefovir in chronic hepatitis B patients

ABSTRACT

An HBsAg-HBIG therapeutic vaccine (Yeast-derived Immune Complexes, YIC) for chronic hepatitis B (CHB) patients has undergone a series of clinical trials. The HBeAg sero-conversion rate of YIC varied from 21.9% to 14% depending on the immunization protocols from 6 to 12 injections. To analyze the immunological mechanisms exerted by 6 injections of YIC, 44 CHB patients were separately immunized with YIC, alum as adjuvant control or normal saline as blank control, with add on of antiviral drug Adefovir in all groups. Kinetic increase in Th1 and Th2 cells CD4⁺ T cell sub-populations with association in decrease in Treg cells and increase of Tc1 and Tc17 cells in CD8⁺ T cells were observed in YIC immunized group. No such changes were found in the other groups. By multifunctional analysis of cytokine profiles, significant increase of IL-2 levels was observed, both in CD4⁺ and CD8⁺ T cells in the YIC immunized group, accompanied by increase in IFN-gamma and decrease of inhibitory factors (IL-10, TGF-β and Foxp3) in CD4⁺ T cells. In the alum immunized group, slight increase of IL-10, TGF-β and Foxp3 in CD4⁺ T cells was found after the second injection, but decreased after more injections, suggesting that alum induced early inflammatory responses to a certain extent. Similar patterns of responses of IL-17A and TNF-α in CD8⁺T cells were shown between YIC and the saline group. Results indicate that add on of Adefovir, did not affect host specific immune responses.

KEYWORDS:

• antigen specific response
• chronic hepatitis B
• immune mechanisms
• multifunctional analysis
• therapeutic vaccine

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We would like to thank the patients enrolled in this study for their participation. We wish to thank the YIC clinical trial study team for their assistance in this work. We are grateful for Dr. Yan Shi for his critical review and proof readings of the manuscript.

Funding

This work was supported by the National Science and Technology Major Projects (2008ZX10002003001, 2012ZX10002002004, 2012ZX10004701 and 2013ZX10002001).