Human monoclonal antibodies as adjuvant treatment of chronic hepatitis B virus infection

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number2290
JournalFrontiers in Immunology
Volume10
Issue numberSEP
DOIs
Publication statusPublished - Sep 1 2019

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Chronic Hepatitis B
Virus Diseases
Hepatitis B virus
Monoclonal Antibodies
Antiviral Agents
Adaptive Immunity
Neutralizing Antibodies
Programmed Cell Death 1 Receptor
T-Lymphocytes
Viral Proteins
Virus Replication
Viral Load
Hepatitis B
Liver Diseases
Hepatocellular Carcinoma
Immunity
Fibrosis
Chronic Disease
Vaccines
Viruses

Keywords

  • Adaptive immunity
  • B cells
  • HBV—hepatitis B virus
  • Human monoclonal antibody
  • Immune system

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Human monoclonal antibodies as adjuvant treatment of chronic hepatitis B virus infection",
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.",
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AU - Cerino, Antonella

AU - Mantovani, Stefania

AU - Mele, Dalila

AU - Oliviero, Barbara

AU - Varchetta, Stefania

AU - Mondelli, Mario U.

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