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Article
Nature Medicine  4, 601 - 606 (1998)
doi:10.1038/nm0598-601

Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans

Julian K.-C. Ma1, 4, Ban Y. Hikmat1, Keith Wycoff2, Nicholas D. Vine1, Daniel Chargelegue1, Lloyd Yu2, Mich B. Hein3 & Thomas Lehner1

  1Department of Immunology, United Medical and Dental Schools, Guy's Hospital, 28th Floor, Guy's Tower, London Bridge, London SE1 9RT, UK. email: J.ma@umds.ac.uk

  2Planet Biotechnology Inc., 2438, Wyandotte Street, Mountain View, CA 94043

  3The Scripps Research Institute, 10550, N. Torrey Pines Road, La Jolla, California 92037, USA

  4Correspondence should be addressed to J.K.−C.M.; e-mail: j.ma@umds.ac.uk

A functional comparison was made between a monoclonal secretory antibody generated in transgenic plants and its parent murine IgC antibody .The affinity constants of both antibodies for a Streptococcus mutans adhesion protein were similar. However the secretory antibody had a higher functional affinity due to its dimeric structure. In the human oral cavity, the secretory antibody survived for up to three days, compared with one day for the IgG antibody. The plant secretory antibody afforded specific protection in humans against oral streptococcal colonization for at least four months. We demonstrate that transgenic plants can be used to produce high affinity, monoclonal secretory antibodies that can prevent specific microbial colonization in humans. These findings could be extended to the immunotherapeutic prevention of other mucosal infections in humans and animals.

REFERENCES
  1. Arntzen, C.J. High-tech herbal medicine: plant-based vaccines [news]. Nature Biotech. 15, 221−222 (1997). | PubMed  | ISI | ChemPort |
  2. Hiatt, A.C., Cafferkey, R. & Bowdish, K. Production of antibodies in transgenic plants. Nature 342, 76−78 (1989). | Article | PubMed  | ISI | ChemPort |
  3. Ma, J.K-C. et al. Generation and assembly of secretory antibodies in plants. Science 268, 716−719 (1995). | PubMed  | ISI | ChemPort |
  4. Lehner, T., Caldwell, J. & Smith, R. Local passive immunization by monoclonal antibodies against streptococcal antigen I/II in the prevention of dental caries. Infect. Immun. 50, 796−799 (1985). | PubMed  | ISI | ChemPort |
  5. Ma, J.K., Smith, R. & Lehner, T. Use of monoclonal antibodies in local passive immunization to prevent colonization of human teeth by Streptococcus mutans. Infect. & Immun. 55, 1274−1278 (1987). | PubMed  | ChemPort |
  6. Ma, J.K-C., Hunjan, M., Smith, R., Kelly, C. & Lehner, T. An investigation into the mechanism of protection by local passive immunisation with monoclonal antibodies against Streptococcus mutans. Infect. Immun. 58, 3407−3414 (1990). | PubMed  | ISI | ChemPort |
  7. Ma, J.K-C., Lehner, T., Stabila, P., Fux, C.I. & Hiatt, A. Assembly of monoclonal antibodies with IgCl and IgA heavy chain domains in transgenic tobacco plants. Eur. J. Immunol. 24, 131−138 (1994). | PubMed  | ISI | ChemPort |
  8. Steward, M.W. & Chargelegue, D. Overview: Measurement and biological significance of antibody affinity and reactivity. In D.M. Weir, L.A. Herzenberg and C.C. Blackwell (eds.), Handbook of experimental immunology, Blackwell Scientific, Oxford, 1997, pp. 38.1.
  9. Underdown, B.J. & Dorrington, K.J. Studies on the structural and conformational basis for the relative resistance of serum and secretory immunoglobulin A to proteolysis. J. Immunol. 112, 949−959 (1974). | PubMed  | ISI | ChemPort |
  10. Mestecky, J. & McGhee, J.R. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv. Immunol. 40, 153−245 (1987) | PubMed  | ISI | ChemPort |
  11. Corthesy, B. Recombinant secretory IgA for immune intervention against mucosal pathogens. Biochem. Soc. Trans. 25, 471−475 (1997) | PubMed  | ISI | ChemPort |
  12. Ma, J.K., Hunjan, M., Smith, R. & Lehner, T. Specificity of monoclonal antibodies in local passive immunization against Streptococcus mutans. Clin. Exper. Immunol. 77, 331−337 (1989) | ISI | ChemPort |
  13. Loe, H. & Silness, J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol. Scand. 21, 532−551 (1963)
  14. Silness, J. & Loe, H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontol. Scand. 22, 121−135 (1964) | PubMed  | ChemPort |
  15. Hajishengallis, G., Nikolova, E. & Russell, M.W. Inhibition of Streptococcus mutans adherence to saliva-coated hydroxyapatite by human secretory immunoglobulin A (S-lgA) antibodies to cell surface protein antigen I/II: reversal by IgAI protease cleavage. Infect. Immun. 60, 5057−5064 (1992) | PubMed  | ISI | ChemPort |
  16. Mazanec, M.B., Lamm, M.E., Lyn, D., Portner, A. & Nedrud, J.G. Comparison of IgA versus IgG monoclonal antibodies for passive immunization of the murine respiratory tract. Vir. Res. 23, 1−12 (1992) | Article | ISI | ChemPort |
  17. Childers, N.K., Bruce, M.G. & McGhee, J.R. Molecular mechanisms of immunoglobulin A defense. Ann. Rev. Microbiol. 43, 503−536 (1989) | Article | ISI | ChemPort |
  18. Mazanec, M.B., Nedrud, J.G., Kaetzel, C.S. & Lamm, M.E. A three-tiered view of the role of IgA in mucosal defense. Immunol. Today 14, 430−435 (1993) | Article | PubMed  | ISI | ChemPort |
  19. Beighton, D., Russell, R.R. & Whiley, R.A. A simple biochemical scheme for the differentiation of Streptococcus mutans and Streptococcus sobrinus. Caries Res. 25, 174−178 (1991) | PubMed  | ISI | ChemPort |
  20. Zylber, L.J. & Jordan, H.V. Development of a selective medium for detection and enumeration of Actinomyces viscosus and Actinomyces naeslundii in dental plaque. J. Clin. Microbiol. 15, 253−259 (1982) | PubMed  | ISI | ChemPort |
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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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