Chimeric monoclonal antibodies to hypervariable region 1 of hepatitis C virus Free

Abstract

Two chimeric monoclonal antibodies (cAbs), 2P24 and 15H4, to hypervariable region 1 (HVR1) of hepatitis C virus (HCV) were constructed by grafting the variable regions of murine monoclonal antibodies (mAbs) 2P24 and 15H4 to a human IgG1 kappa constant region. Two cAb-producing cell lines were adapted to serum-free media. Both cAb 2P24 and cAb 15H4 cell lines produced 3–5 μg antibodies ml after 3–5 days culture. cAbs retained binding characteristics similar to those observed in the original mAbs. There was no clear difference in affinity between binding of cAbs and mAbs to seven HVR1 peptides. Mixtures of biotinylated cAbs or mAbs reacted with 32 (86 %) and 31 (84 %) of 37 HVR1 peptides, respectively, but not with non-HVR1 control peptides. HCV from 16 out of 18 (89 %) random HCV-containing plasmas was captured by the mixture of biotinylated cAbs. The capture from IgG-depleted plasmas suggested that cAbs captured mainly free rather than complexed HCV, irrespective of genotype. A mixture of the two cAbs inhibited HCV binding to Molt-4 cells in a dose-dependent manner. These cAbs may be useful for prevention of nosocomial HCV infection and passive immunization to prevent HCV reinfection after liver transplantation.

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2005-06-01
2024-03-28
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References

  1. Allander T., Drakenberg K., Beyene A., Rosa D., Abrignani S., Houghton M., Widell A., Grillner L., Persson M. A. A. 2000; Recombinant human monoclonal antibodies against different conformational epitopes of the E2 envelope glycoprotein of hepatitis C virus that inhibit its interaction with CD81. J Gen Virol81:2451–2459
    [Google Scholar]
  2. Basu A., Beyene A., Meyer K., Ray R. 2004; The hypervariable region 1 of the E2 glycoprotein of hepatitis C virus binds to glycosaminoglycans, but this binding does not lead to infection in a pseudotype system. J Virol 78:4478–4486 [CrossRef]
    [Google Scholar]
  3. Bruggemann M., Williams G. T., Bindon C. I., Clark M. R., Walker M. R., Jefferis R., Waldmann H., Neuberger M. S. 1987; Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med 166:1351–1361 [CrossRef]
    [Google Scholar]
  4. Candotti D., Temple J., Sarkodie F., Allain J.-P. 2003; Frequent recovery and broad genotype 2 diversity characterize hepatitis C virus infection in Ghana, West Africa. J Virol 77:7914–7923 [CrossRef]
    [Google Scholar]
  5. Casadevall A., Dadachova E., Pirofski L. A. 2004; Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2:695–703 [CrossRef]
    [Google Scholar]
  6. Cerino A., Meola A., Segagni L., Furione M., Marciano S., Triyatni M., Liang T. J., Nicosia A., Mondelli M. U. 2001; Monoclonal antibodies with broad specificity for hepatitis C virus hypervariable region 1 variants can recognize viral particles. J Immunol 167:3878–3886 [CrossRef]
    [Google Scholar]
  7. Clark M. 2000; Antibody humanization: a case of the ‘Emperor's new clothes’?. Immunol Today 21:397–402 [CrossRef]
    [Google Scholar]
  8. Crabb C. 2001; Hard-won advances spark excitement about hepatitis C. Science 294:506–507 [CrossRef]
    [Google Scholar]
  9. Esumi M., Ahmed M., Zhou Y.-H., Takahashi H., Shikata T. 1998; Murine antibodies against E2 and hypervariable region 1 cross-reactively capture hepatitis C virus. Virology 251:158–164 [CrossRef]
    [Google Scholar]
  10. Farci P., Alter H. J., Wong D. C., Miller R. H., Govindarajan S., Engle R., Shapiro M., Purcell R. H. 1994; Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization. Proc Natl Acad Sci U S A 91:7792–7796 [CrossRef]
    [Google Scholar]
  11. Farci P., Shimoda A., Wong D. 7 other authors 1996; Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. Proc Natl Acad Sci U S A 93:15394–15399 [CrossRef]
    [Google Scholar]
  12. Fried M. W., Hoofnagle J. H. 1995; Therapy of hepatitis C. Semin Liver Dis 15:82–91 [CrossRef]
    [Google Scholar]
  13. Furtado P. B., McElveen J. E., Gough L., Armour K. L., Clark M. R., Sewell H. F., Shakib F. 2002; The production and characterisation of a chimaeric human IgE antibody, recognising the major mite allergen Der p 1, and its chimaeric human IgG1 anti-idiotype. Mol Pathol 55:315–324 [CrossRef]
    [Google Scholar]
  14. Gura T. 2002; Magic bullets hit the target. Nature 417:584–586 [CrossRef]
    [Google Scholar]
  15. Hamaia S., Li C., Allain J.-P. 2001; The dynamics of hepatitis C virus binding to platelets and 2 mononuclear cell lines. Blood 98:2293–2300 [CrossRef]
    [Google Scholar]
  16. Jackson P., Petrik J., Alexander G. J. M., Pearson G., Allain J.-P. 1997; Reactivity of synthetic peptides representing selected sections of hepatitis C virus core and envelope proteins with a panel of hepatitis C virus-seropositive human plasma. J Med Virol 51:67–79 [CrossRef]
    [Google Scholar]
  17. Jones P. T., Dear P. H., Foote J., Neuberger M. S., Winter G. 1986; Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321:522–525 [CrossRef]
    [Google Scholar]
  18. Kabat E. A., Wu T. T., Perry H. M., Gottesman K. S., Foeller C. 1991 Sequences of Proteins of Immunological Interest , 5th edn. Bethesda, MD: US Department of Health and Human Services;
    [Google Scholar]
  19. Köhler G., Milstein C. 1975; Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497 [CrossRef]
    [Google Scholar]
  20. Korenaga M., Hino K., Katoh Y., Yamaguchi Y., Okuda M., Yoshioka K., Okita K. 2001; A possible role of hypervariable region 1 quasispecies in escape of hepatitis C virus particles from neutralization. J Viral Hepat 8:331–340 [CrossRef]
    [Google Scholar]
  21. Kumar U., Monjardino J., Thomas H. C. 1994; Hypervariable region of hepatitis C virus envelope glycoprotein (E2/NS1) in an agammaglobulinemic patient. Gastroenterology 106:1072–1075
    [Google Scholar]
  22. Kurihara C., Tsuzuki Y., Hokari R. 7 other authors 2004; A highly hydrophobic domain within hypervariable region 1 may be related to the entry of hepatitis C virus into cultured human hepatoma cells. J Med Virol 74:546–555 [CrossRef]
    [Google Scholar]
  23. Lavanchy D., McMahon B. 2000; Worldwide prevalence and prevention of hepatitis C. In Hepatitis C pp  185–201 Edited by Liang T. J., Hoofnagle J. H. San Diego: Academic Press;
    [Google Scholar]
  24. Li C., Candotti D., Allain J.-P. 2001; Production and characterization of monoclonal antibodies specific for a conserved epitope within hepatitis C virus hypervariable region 1. J Virol 75:12412–12420 [CrossRef]
    [Google Scholar]
  25. McHutchison J. G., Gordon S. C., Schiff E. R. 7 other authors 1998; Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 339:1485–1492 [CrossRef]
    [Google Scholar]
  26. Mondelli M. U., Cerino A., Lisa A. 11 other authors 1999; Antibody responses to hepatitis C virus hypervariable region 1: evidence for cross-reactivity and immune-mediated sequence variation. Hepatology 30:537–545 [CrossRef]
    [Google Scholar]
  27. Mondelli M. U., Cerino A., Meola A., Nicosia A. 2003; Variability or conservation of hepatitis C virus hypervariable region 1? Implications for immune responses. J Biosci 28:305–310 [CrossRef]
    [Google Scholar]
  28. Penin F., Combet C., Germanidis G., Frainais P.-O., Deléage G., Pawlotsky J.-M. 2001; Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment. J Virol 75:5703–5710 [CrossRef]
    [Google Scholar]
  29. Petrik J., Pearson G. J. M., Allain J.-P. 1997; High throughput PCR detection of HCV based on semiautomated multisample RNA capture. J Virol Methods 64:147–159 [CrossRef]
    [Google Scholar]
  30. Puntoriero G., Meola A., Lahm A. 9 other authors 1998; Towards a solution for hepatitis C virus hypervariability: mimotopes of the hypervariable region 1 can induce antibodies cross-reacting with a large number of viral variants. EMBO J 17:3521–3533 [CrossRef]
    [Google Scholar]
  31. Ray S. C., Wang Y.-M., Laeyendecker O., Ticehurst J. R., Villano S. A., Thomas D. L. 1999; Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as a decoy. J Virol 73:2938–2946
    [Google Scholar]
  32. Rosa D., Campagnoli S., Moretto C. 11 other authors 1996; A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. Proc Natl Acad Sci U S A 93:1759–1763 [CrossRef]
    [Google Scholar]
  33. Scarselli E., Ansuini H., Cerino R. 7 other authors 2002; The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21:5017–5025 [CrossRef]
    [Google Scholar]
  34. Shang D., Zhai W., Allain J.-P. 1999; Broadly cross-reactive, high-affinity antibody to hypervariable region 1 of the hepatitis C virus in rabbits. Virology 258:396–405 [CrossRef]
    [Google Scholar]
  35. Shimizu Y. K., Hijikata M., Iwamoto A., Alter H. J., Purcell R. H., Yoshikura H. 1994; Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses. J Virol 68:1494–1500
    [Google Scholar]
  36. Triyatni M., Vergalla J., Davis A. R., Hadlock K. G., Foung S. K. H., Liang T. J. 2002; Structural features of envelope proteins on hepatitis C virus-like particles as determined by anti-envelope monoclonal antibodies and CD81 binding. Virology 298:124–132 [CrossRef]
    [Google Scholar]
  37. van Doorn L.-J., Capriles I., Maertens G., Deleys R., Murray K., Kos T., Schellekens H., Quint W. 1995; Sequence evolution of the hypervariable region in the putative envelope region E2/NS1 of hepatitis C virus is correlated with specific humoral responses. J Virol 69:773–778
    [Google Scholar]
  38. Watanabe K., Yoshioka K., Ito H. 8 other authors 1999; The hypervariable region 1 protein of hepatitis C virus broadly reactive with sera of patients with chronic hepatitis C has a similar amino acid sequence with the consensus sequence. Virology 264:153–158 [CrossRef]
    [Google Scholar]
  39. World Health Organization 1999; Global surveillance and control of hepatitis C. Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp. Belgium. J Viral Hepat 6:35–47 [CrossRef]
    [Google Scholar]
  40. Yanagi M., Purcell R. H., Emerson S. U., Bukh J. 1997; Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee. Proc Natl Acad Sci U S A 94:8738–8743 [CrossRef]
    [Google Scholar]
  41. Zhai W., Davies J., Shang D. Z., Chan S. W., Allain J.-P. 1999; Human recombinant single-chain antibody fragments, specific for the hypervariable region 1 of hepatitis C virus, from immune phage-display libraries. J Viral Hepat 6:115–124 [CrossRef]
    [Google Scholar]
  42. Zhou Y.-H., Shimizu Y. K., Esumi M. 2000; Monoclonal antibodies to the hypervariable region 1 of hepatitis C virus capture virus and inhibit virus adsorption to susceptible cells in vitro . Virology 269:276–283 [CrossRef]
    [Google Scholar]
  43. Zibert A., Schreier E., Roggendorf M. 1995; Antibodies in human sera specific to hypervariable region 1 of hepatitis C virus can block viral attachment. Virology 208:653–661 [CrossRef]
    [Google Scholar]
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