Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees

Rachel Eren; Ehud Ilan; Ofer Nussbaum; Ido Lubin; Dov Terkieltaub; Yossi Arazi; Ofer Ben-Moshe; Alberto Kitchinzky; Shoshana Berr; Judy Gopher; Arie Zauberman; Eithan Galun; Danny Shouval; Nili Daudi; Ahamed Eid; Oded Jurim; Lars O. Magnius; Berit Hammas; Yair Reisner; Shlomo Dagan

doi:10.1053/jhep.2000.9632

Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees

Rachel Eren, Ehud Ilan, Ofer Nussbaum, Ido Lubin, Dov Terkieltaub, Yossi Arazi, Ofer Ben-Moshe, Alberto Kitchinzky, Shoshana Berr, Judy Gopher, Arie Zauberman, Eithan Galun, Danny Shouval, Nili Daudi, Ahamed Eid, Oded Jurim, Lars O. Magnius, Berit Hammas, Yair Reisner, Shlomo Dagan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10^-10 mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications.

Original language	English
Pages (from-to)	588-596
Number of pages	9
Journal	Hepatology
Volume	32
Issue number	3
DOIs	https://doi.org/10.1053/jhep.2000.9632
State	Published - 2000
Externally published	Yes

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Eren, R., Ilan, E., Nussbaum, O., Lubin, I., Terkieltaub, D., Arazi, Y., Ben-Moshe, O., Kitchinzky, A., Berr, S., Gopher, J., Zauberman, A., Galun, E., Shouval, D., Daudi, N., Eid, A., Jurim, O., Magnius, L. O., Hammas, B., Reisner, Y., & Dagan, S. (2000). Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees. Hepatology, 32(3), 588-596. https://doi.org/10.1053/jhep.2000.9632

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title = "Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees",

abstract = "Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10-10 mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications.",

author = "Rachel Eren and Ehud Ilan and Ofer Nussbaum and Ido Lubin and Dov Terkieltaub and Yossi Arazi and Ofer Ben-Moshe and Alberto Kitchinzky and Shoshana Berr and Judy Gopher and Arie Zauberman and Eithan Galun and Danny Shouval and Nili Daudi and Ahamed Eid and Oded Jurim and Magnius, {Lars O.} and Berit Hammas and Yair Reisner and Shlomo Dagan",

year = "2000",

doi = "10.1053/jhep.2000.9632",

language = "אנגלית",

volume = "32",

pages = "588--596",

journal = "Hepatology",

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Eren, R, Ilan, E, Nussbaum, O, Lubin, I, Terkieltaub, D, Arazi, Y, Ben-Moshe, O, Kitchinzky, A, Berr, S, Gopher, J, Zauberman, A, Galun, E, Shouval, D, Daudi, N, Eid, A, Jurim, O, Magnius, LO, Hammas, B, Reisner, Y & Dagan, S 2000, 'Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees', Hepatology, vol. 32, no. 3, pp. 588-596. https://doi.org/10.1053/jhep.2000.9632

TY - JOUR

T1 - Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees

AU - Eren, Rachel

AU - Ilan, Ehud

AU - Nussbaum, Ofer

AU - Lubin, Ido

AU - Terkieltaub, Dov

AU - Arazi, Yossi

AU - Ben-Moshe, Ofer

AU - Kitchinzky, Alberto

AU - Berr, Shoshana

AU - Gopher, Judy

AU - Zauberman, Arie

AU - Galun, Eithan

AU - Shouval, Danny

AU - Daudi, Nili

AU - Eid, Ahamed

AU - Jurim, Oded

AU - Magnius, Lars O.

AU - Hammas, Berit

AU - Reisner, Yair

AU - Dagan, Shlomo

PY - 2000

Y1 - 2000

N2 - Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10-10 mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications.

AB - Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10-10 mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications.

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SN - 0270-9139

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JF - Hepatology

IS - 3

ER -

Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees

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