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. 2019 Sep 25:10:2290.
doi: 10.3389/fimmu.2019.02290. eCollection 2019.

Human Monoclonal Antibodies as Adjuvant Treatment of Chronic Hepatitis B Virus Infection

Antonella Cerino  1 , Stefania Mantovani  1 , Dalila Mele  1 , Barbara Oliviero  1 , Stefania Varchetta  1 , Mario U Mondelli  1   2
Affiliations

Human Monoclonal Antibodies as Adjuvant Treatment of Chronic Hepatitis B Virus Infection

Antonella Cerino et al. Front Immunol. .

Abstract

Despite the availability of an effective prophylactic vaccine leading to sterilizing immunity, hepatitis B virus (HBV) is responsible for chronic liver disease in more than 250 million individuals, potentially leading to cirrhosis and hepatocellular carcinoma. Antiviral drugs able to completely suppress virus replication are indeed available but they are, by and large, unable to eradicate the virus. Several alternative new treatment approaches are currently being developed but none have so far captured the interest of clinicians for possible clinical development. A constant feature of chronic HBV infection is T-cell exhaustion resulting from persistent exposure to high antigen concentrations as shown by the high expression of programmed cell death protein 1 (PD-1) by HBV-specific CD8 T cells. One way of tackling this problem is to develop HBV-specific neutralizing antibodies that would clear excess envelope proteins from the circulation, allowing for nucleos(t)ide analogs or other antiviral drugs now in preclinical and early clinical development to take advantage of a reconstituted adaptive immunity. Several fully human monoclonal antibodies (mAb) have been developed from HBV-vaccinated and subjects convalescent from acute hepatitis B that show different properties and specificities. It is envisaged that such neutralizing mAb may be used as adjuvant treatment to reduce viral protein load, thus rescuing adaptive immunity in an effort to optimize the effect of antiviral drugs.

Keywords: B cells; HBV—hepatitis B virus; adaptive immunity; human monoclonal antibody; immune system.

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Figures

Figure 1
Figure 1
Effect of HBV infection on immune responses. (A) Infected hepatocytes produce and release large amounts of HBV envelope polypeptides also expressed on HB virions which suppress adaptive immune responses. (B) Human monoclonal antibodies specific for HBV envelope proteins (HBs-humAbs) may reduce peripheral protein load allowing restoration of B and T cell-mediated immune responses.
Figure 2
Figure 2
Combined or sequential treatment of chronic HBV infection with HBsAg-specific humAbs and nucleos(t)ide analogs. Patients with chronic HBV infection (gray) can be treated with HBs-humAbs to rescue T and B cell exhaustion caused by HBV envelope proteins, either sequentially or in combination with nucleos(t)ide analogs (NUCs). Reconstitution of HBV-specific adaptive immunity would ultimately increase NUC efficacy and result in viral clearance (green). T-eff, T effector cells.
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