Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response.

Zhiyong Ma,Shicheng Gao,Ejuan Zhang,Mengji Lu,Yong Xiong

doi:10.3389/fimmu.2019.02308

Abstract

The central role of the cellular immune response in the control and clearance of the hepatitis B virus (HBV) infection has been well-established. The contribution of humoral immunity, including B cell and antibody responses against HBV, has been investigated for a long time but has attracted increasing attention again in recent years. The anti-HBs antibody was first recognized as a marker of protective immunity after the acute resolution of the HBV infection (or vaccination) and is now defined as a biomarker for the functional cure of chronic hepatitis B (CHB). In this way, therapies targeting HBV-specific B cells and the induction of an anti-HBs antibody response are essential elements of a rational strategy to terminate chronic HBV infection. However, a high load of HBsAg in the blood, which has been proposed to induce antigen-specific immune tolerance, represents a major obstacle to curing CHB. Long-term antiviral treatment by nucleoside analogs, by targeting viral translation by siRNA, by inhibiting HBsAg release via nucleic acid polymers, or by neutralizing HBsAg via specific antibodies could potentially reduce the HBsAg load in CHB patients. A combined strategy including a reduction of the HBsAg load via the above treatments and the therapeutic targeting of B cells by vaccination may induce the appearance of anti-HBs antibodies and lead to a functional cure of CHB.

Highlights

It is estimated that more than 250 million people worldwide are chronically infected with the hepatitis B virus (HBV), and over 887,000 deaths are caused by HBV infection annually due to the disease’s complications, such as cirrhosis and hepatocellular carcinoma (HCC) [1, 2]
This study implied that a combination strategy with antiviral treatment and antibody mediated immunotherapy, followed by triggering a B cell response through vaccination may lead to a sustained loss of HBV surface antigen (HBsAg) and a functional cure for chronic hepatitis B (CHB)
Current antiviral therapies with Peg-IFN and nucleos(t)ide analogs (NAs) can suppress HBV replication and improve the prognosis of CHB, but they can hardly clear HBsAg to achieve a functional cure of CHB

Summary

Introduction

It is estimated that more than 250 million people worldwide are chronically infected with the hepatitis B virus (HBV), and over 887,000 deaths are caused by HBV infection annually due to the disease’s complications, such as cirrhosis and hepatocellular carcinoma (HCC) [1, 2]. Given the importance of anti-HBs in preventing and curing HBV infection, several groups have attempted to detect the HBsAg-specific memory B cell response using different methods in vaccinated people and CHB patients.

Results

Conclusion