activity of a mixture of two human monoclonal antibodies (anti-HBs) in a chronic hepatitis B virus carrier chimpanzee Free

Abstract

A 35-year-old female hepatitis B virus carrier chimpanzee was infused with one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B (antibodies against hepatitis B virus surface antigen; HBsAg). Blood samples were taken before and up to 3 weeks after infusion. HBsAg and antibodies against HBsAg (anti-HBs) were quantified by radioimmunoassay and enzyme immunoassay. Free anti-HBs was never detected. Thirty min after the start of the infusion the HBsAg level was minimal with maximum loading of the chimpanzee HBsAg with human immunoglobulin. HBsAg complexes could be dissociated by acid treatment. The HBsAg level was completely restored on day 7. Similar results were obtained for the preS1-containing particles that may represent the infectious viral particles in the chimpanzee serum. A mouse monoclonal anti-HBs (HBs.OT40) was found to compete with 9H9 in artificial immune complexes with the pre-treatment HBsAg from the chimpanzee. Used as a conjugate, HBs.OT40 yielded a maximum decrease in the signal in the 30 min sample compared to non-competing anti-HBs conjugates. This indicates binding of HBsAg with 9H9 in the circulation of the chimpanzee. Immune-complexed 4-7B could not be detected by its corresponding 4-7B peptide conjugate, probably due to its low concentration in the complexes. It is concluded that human monoclonal anti-HBs can effectively reduce the level of HBsAg in serum from this chronic carrier. Monoclonals 9H9 and 4-7B may complement each other due to their different mechanisms of inactivation, probably with higher efficiency than that monitored by our HBsAg screening assays.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-6-1529
1999-06-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/6/0801529a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-6-1529&mimeType=html&fmt=ahah

References

  1. Bartholomew M. M., Jansen R. W., Jeffers L. J., Reddy K. R., Johnson L. C., Bunzendahl H., Condraeay L. D., Tzakis A. G., Schgiff E. R., Brown N. A. 1997; Hepatitis -B-virus resistance to lamivudine given for recurrent infection after orthotopic liver transplantation. Lancet 349:20–23
    [Google Scholar]
  2. Busstra M., de Man R. A., Heijtink R. A., Voermans J., Schalm S. W., Osterhaus A. D. M. E. 1995; Failure of HBIg therapy after HBV related OLT is due to a reduction of HBsAg neutralisation [Abstract]. Journal of Hepatology 23: (suppl. 1) 103
    [Google Scholar]
  3. Carman W. F., Trautwein C., van Deursen F. J., Colman K., Dornan E., McIntyre G., Waters J., Kliem V., Muller R., Thomas H. C., Manns M. P. 1996; Hepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis. Hepatology 24:489–493
    [Google Scholar]
  4. Ehrlich P. H., Moustafa Z. A., Justice J. C., Harfeldt K. E., Kelley R.L., Ostberg L. 1992; Characterization of human monoclonal antibodies directed against hepatitis B surface antigen. Human Antibodies and Hybridomas 3:2–7
    [Google Scholar]
  5. Heijtink R. A., Kruining J., Weber Y. A. M., de Man R. A., Schalm S. W. 1995; Anti-hepatitis B virus activity of a mixture of two monoclonal antibodies in an ‘inhibition in solution assay’. Hepatology 22:l078–l083
    [Google Scholar]
  6. Itoh Y., Fujisawa Y. 1986; Synthesis in yeast of hepatitis B virus surface antigen modified P31 particles by gene modification. Biochemical and Biophysical Research Communications 141:942–948
    [Google Scholar]
  7. Nishanian P., Huskins K. R., Stehn S., Detels R., Fahey J. L. 1990; A simple method for improved assay demonstrates that HIV p24 antigen is present as immune complexes in most sera from HIV-infected individuals. Journal of Infectious Diseases 162:21–28
    [Google Scholar]
  8. Oon C.-J., Tan K.-L., Harrison T., Zuckerman A. 1996; Natural history of hepatitis B surface antigen mutants in children. Lancet 348:1524
    [Google Scholar]
  9. Petit M. A., Capel F., Riottot M. M., Dauguet C., Pillot J. 1987; Antigenic mapping of the surface proteins of infectious hepatitis B virus particles. Journal of General Virology 68:2759–2767
    [Google Scholar]
  10. Samuel D., Muller R., Alexander G., Fassati L., Ducot B., Benhamou J. P., Bismuth H. & the Investigators of the European Concerned Action on Viral Hepatitis Study 1993; Liver transplantation in European patients with the hepatitis B surface antigen. New England Journal of Medicine 329:1842–1847
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-6-1529
Loading
/content/journal/jgv/10.1099/0022-1317-80-6-1529
Loading

Data & Media loading...

Most cited Most Cited RSS feed