Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

Nature Medicine volume 4, pages 601–606 (1998)Cite this article

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Arntzen, C.J. High-tech herbal medicine: plant-based vaccines [news]. Nature Biotech. 15, 221–222 (1997).

    Article  CAS  Google Scholar 

  2. Hiatt, A.C., Cafferkey, R. & Bowdish, K. Production of antibodies in transgenic plants. Nature 342, 76–78 (1989).

    Article  CAS  Google Scholar 

  3. Ma, J.K-C. et al. Generation and assembly of secretory antibodies in plants. Science 268, 716–719 (1995).

    Article  CAS  Google Scholar 

  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  PubMed Central  CAS  Google Scholar 

  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).

    CAS  Google Scholar 

  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  PubMed Central  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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.

    Google Scholar 

  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  CAS  Google Scholar 

  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)

    Article  CAS  Google Scholar 

  11. Corthesy, B. Recombinant secretory IgA for immune intervention against mucosal pathogens. Biochem. Soc. Trans. 25, 471–475 (1997)

    Article  CAS  Google Scholar 

  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)

    CAS  Google Scholar 

  13. Loe, H. & Silness, J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol. Scand. 21, 532–551 (1963)

    Article  Google Scholar 

  14. Silness, J. & Loe, H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontol. Scand. 22, 121–135 (1964)

    Article  CAS  Google Scholar 

  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  PubMed Central  CAS  Google Scholar 

  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  CAS  Google Scholar 

  17. Childers, N.K., Bruce, M.G. & McGhee, J.R. Molecular mechanisms of immunoglobulin A defense. Ann. Rev. Microbiol. 43, 503–536 (1989)

    Article  CAS  Google Scholar 

  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  CAS  Google Scholar 

  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)

    Article  CAS  Google Scholar 

  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  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, United Medical and Dental Schools, Guy's Hospital, 28th Floor, Guy's Tower, London Bridge, London, SE1 9RT, UK

    Julian K.-C. Ma, Ban Y. Hikmat, Nicholas D. Vine, Daniel Chargelegue & Thomas Lehner

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

    Keith Wycoff & Lloyd Yu

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

    Mich B. Hein

Authors
  1. Julian K.-C. Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ban Y. Hikmat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keith Wycoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicholas D. Vine
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel Chargelegue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lloyd Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mich B. Hein
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thomas Lehner
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, JC., Hikmat, B., Wycoff, K. et al. Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med 4, 601–606 (1998). https://doi.org/10.1038/nm0598-601

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0598-601

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing