Front Immunol. 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.
Cerino A1, Mantovani S1, Mele D1, Oliviero B1, Varchetta S1, Mondelli MU1,2.
Author information
1
S.C. di Malattie Infettive II - Infettivologia e Immunologia, Dipartimento di Scienze Mediche e Malattie Infettive, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
2
Dipartimento di Medicina Interna e Terapia Medica, Università di Pavia, Pavia, Italy.
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.
1个
S.C. di Malattie Infettive II-Infettivologia e Immunologia，Dipartimento di Scienze Mediche e Malattie Infettive，Fondazione IRCCS Policlinico San Matteo，意大利帕维亚。
2
意大利国际医疗卫生部，意大利帕维亚大学帕维亚分校。