Viral Hepatitis

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Novel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells†

  1. Avidan U. Neumann1,
  2. Sandra Phillips2,
  3. Idit Levine1,
  4. Samreen Ijaz3,
  5. Harel Dahari1,4,
  6. Rachel Eren5,‡,
  7. Shlomo Dagan5,‡,
  8. Nikolai V. Naoumov2,§,¶,*

Article first published online: 25 MAY 2010

DOI: 10.1002/hep.23778

Issue

Hepatology

Hepatology

Volume 52, Issue 3, pages 875–885, September 2010

Additional Information

How to Cite

Neumann, A. U., Phillips, S., Levine, I., Ijaz, S., Dahari, H., Eren, R., Dagan, S. and Naoumov, N. V. (2010), Novel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells. Hepatology, 52: 875–885. doi: 10.1002/hep.23778

Author Information

  1. 1

    Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel

  2. 2

    Institute of Hepatology, University College London, London, United Kingdom

  3. 3

    Hepatitis Laboratory, Health Protection Agency, Colindale, United Kingdom

  4. 4

    Department of Medicine, Section of Hepatology, University of Illinois at Chicago, Chicago, IL

  5. 5

    XTL Biopharmaceuticals, Ltd., Kiryat Weizmann Science Park, Rehovot, Israel

  1. ‡

    Andromeda Biotech, Ltd., Yavne 81227, Israel

  2. §

    Novartis Pharma, Basel, Switzerland

  1. fax: +41-61-3240845

*Immunology and Infectious Diseases, Novartis Pharma AG, Fabrikstrasse 6, Basel 4002, Switzerland

  1. †

    Dr. Neumann is on the speakers' bureau of and received grants from Roche, Merck, and Human Genome Sciences. Dr. Ijaz received royalties from Abbott Murex.

  2. fax: +41-61-3240845

Publication History

  1. Issue published online: 26 AUG 2010
  2. Article first published online: 25 MAY 2010
  3. Manuscript Accepted: 17 MAY 2010
  4. Manuscript Received: 8 SEP 2009

Funded by

  • University of Illinois Walter Payton Liver Center GUILD and by NIH grant. Grant Number: P20-RR018754

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Abstract

Antibodies are thought to exert antiviral activities by blocking viral entry into cells and/or accelerating viral clearance from circulation. In particular, antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) confer protection, by binding circulating virus. Here, we used mathematical modeling to gain information about viral dynamics during and after single or multiple infusions of a combination of two human monoclonal anti-HBs (HepeX-B) antibodies in patients with chronic hepatitis B. The antibody HBV-17 recognizes a conformational epitope, whereas antibody HBV-19 recognizes a linear epitope on the HBsAg. The kinetic profiles of the decline of serum HBV DNA and HBsAg revealed partial blocking of virion release from infected cells as a new antiviral mechanism, in addition to acceleration of HBV clearance from the circulation. We then replicated this approach in vitro, using cells secreting HBsAg, and compared the prediction of the mathematical modeling obtained from the in vivo kinetics. In vitro, HepeX-B treatment of HBsAg-producing cells showed cellular uptake of antibodies, resulting in intracellular accumulation of viral particles. Blocking of HBsAg secretion also continued after HepeX-B was removed from the cell culture supernatants. Conclusion: These results identify a novel antiviral mechanism of antibodies to HBsAg (anti-HBs) involving prolonged blocking of the HBV and HBsAg subviral particles release from infected cells. This may have implications in designing new therapies for patients with chronic HBV infection and may also be relevant in other viral infections. (HEPATOLOGY 2010;)

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