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. 1996 Feb;64(2):422–427. doi: 10.1128/iai.64.2.422-427.1996

Passive immunization with monoclonal antibodies against Porphyromonas gingivalis in patients with periodontitis.

V Booth 1, F P Ashley 1, T Lehner 1
PMCID: PMC173780  PMID: 8550186

Abstract

Selective inhibition of recolonization of Porphyromonas gingivalis was investigated by topical application of monoclonal antibody (MAb). To select a MAb to P. gingivalis with the potential for recognizing most strains of P. gingivalis, we examined seven MAbs, one of which (MAb 61BG 1.3) recognized all 22 laboratory strains and serotypes of P. gingivalis tested as well as 105 human clinical isolates. A comparative study of the number of P. gingivalis bacteria identified by conventional culture and immunofluorescence with MAb 61BG 1.3 showed a very significant correlation between the two methods (Spearman r = 0.85, P < 0.001). Fourteen patients with periodontitis, who harbored P. gingivalis in their subgingival plaque, were treated by root planing and with metronidazole to suppress any detectable P. gingivalis. In this double-blind study, the patients were then divided randomly into two groups; one was treated with MAb to P. gingivalis, and the other was treated with saline. Each patient had four subgingival applications of 3 micrograms of MAb (or saline) per tooth at 1, 3, 7, and 10 days after P. gingivalis was suppressed. The number of P. gingivalis bacteria was then monitored, and significantly less recolonization of the sites with the most severe periodontitis was found in the MAb-treated patients than in the control patients (P < 0.01). This was evident at 6 and 9 months after the application of MAb, but by 12 months, P. gingivalis, was also found to recolonize these sites in two of the MAb-treated patients. The effect of MAb was specific to P. gingivalis, since the numbers of spirochetes were not significantly different between the two groups. However, no significant difference in any clinical periodontal indices between the immunized and control patients at 6 and 12 months was observed. This is the first demonstration that a putative periodontal pathogen can be selectively prevented from recolonization for up to 9 months in sites with the most severe periodontitis. This strategy could be used to establish directly in humans whether a microorganism is involved in the pathogenesis of periodontitis, by repeated application of the corresponding MAb at about 6-month intervals and by comparing the clinical indices between the MAb-treated and control patients.

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Selected References

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  1. Ashley F. P., Gallagher J., Wilson R. F. The occurrence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, Bacteroides intermedius and spirochaetes in the subgingival microflora in relation to the early onset of periodontitis in a group of adolescents. Oral Microbiol Immunol. 1989 Dec;4(4):236–238. doi: 10.1111/j.1399-302x.1989.tb00260.x. [DOI] [PubMed] [Google Scholar]
  2. Bramanti T. E., Holt S. C. Roles of porphyrins and host iron transport proteins in regulation of growth of Porphyromonas gingivalis W50. J Bacteriol. 1991 Nov;173(22):7330–7339. doi: 10.1128/jb.173.22.7330-7339.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ebersole J. L., Brunsvold M., Steffensen B., Wood R., Holt S. C. Effects of immunization with Porphyromonas gingivalis and Prevotella intermedia on progression of ligature-induced periodontitis in the nonhuman primate Macaca fascicularis. Infect Immun. 1991 Oct;59(10):3351–3359. doi: 10.1128/iai.59.10.3351-3359.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gallois Y., Vol S., Cacès E., Balkau B. Distribution of fasting serum insulin measured by enzyme immunoassay in an unselected population of 4,032 individuals. Reference values according to age and sex. D.E.S.I.R. Study Group. Données Epidémiologiques sur le Syndrome d'Insulino-Résistance. Diabetes Metab. 1996 Dec;22(6):427–431. [PubMed] [Google Scholar]
  5. Gmür R. Applicability of monoclonal antibodies to quantitatively monitor subgingival plaque for specific bacteria. Oral Microbiol Immunol. 1988 Dec;3(4):187–191. doi: 10.1111/j.1399-302x.1988.tb00008.x. [DOI] [PubMed] [Google Scholar]
  6. Gmür R., Werner-Felmayer G., Guggenheim B. Production and characterization of monoclonal antibodies specific for Bacteroides gingivalis. Oral Microbiol Immunol. 1988 Dec;3(4):181–186. doi: 10.1111/j.1399-302x.1988.tb00007.x. [DOI] [PubMed] [Google Scholar]
  7. Goodson J. M., Tanner A. C., Haffajee A. D., Sornberger G. C., Socransky S. S. Patterns of progression and regression of advanced destructive periodontal disease. J Clin Periodontol. 1982 Nov;9(6):472–481. doi: 10.1111/j.1600-051x.1982.tb02108.x. [DOI] [PubMed] [Google Scholar]
  8. Gusberti F. A., Syed S. A., Lang N. P. Combined antibiotic (metronidazole) and mechanical treatment effects on the subgingival bacterial flora of sites with recurrent periodontal disease. J Clin Periodontol. 1988 Jul;15(6):353–359. doi: 10.1111/j.1600-051x.1988.tb01011.x. [DOI] [PubMed] [Google Scholar]
  9. Holt S. C., Bramanti T. E. Factors in virulence expression and their role in periodontal disease pathogenesis. Crit Rev Oral Biol Med. 1991;2(2):177–281. doi: 10.1177/10454411910020020301. [DOI] [PubMed] [Google Scholar]
  10. Holt S. C., Ebersole J., Felton J., Brunsvold M., Kornman K. S. Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. Science. 1988 Jan 1;239(4835):55–57. doi: 10.1126/science.3336774. [DOI] [PubMed] [Google Scholar]
  11. Horowitz B., Wiebe M. E., Lippin A., Stryker M. H. Inactivation of viruses in labile blood derivatives. I. Disruption of lipid-enveloped viruses by tri(n-butyl)phosphate detergent combinations. Transfusion. 1985 Nov-Dec;25(6):516–522. doi: 10.1046/j.1537-2995.1985.25686071422.x. [DOI] [PubMed] [Google Scholar]
  12. 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. 1985 Dec;50(3):796–799. doi: 10.1128/iai.50.3.796-799.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lehner T., Ma J. K., Kelly C. G. A mechanism of passive immunization with monoclonal antibodies to a 185,000 M(r) streptococcal antigen. Adv Exp Med Biol. 1992;327:151–163. doi: 10.1007/978-1-4615-3410-5_17. [DOI] [PubMed] [Google Scholar]
  14. Loesche W. J., Hockett R. N., Syed S. A. The predominant cultivable flora of tooth surface plaque removed from institutionalized subjects. Arch Oral Biol. 1972 Sep;17(9):1311–1325. doi: 10.1016/0003-9969(72)90164-1. [DOI] [PubMed] [Google Scholar]
  15. Loesche W. J., Syed S. A., Morrison E. C., Kerry G. A., Higgins T., Stoll J. Metronidazole in periodontitis. I. Clinical and bacteriological results after 15 to 30 weeks. J Periodontol. 1984 Jun;55(6):325–335. doi: 10.1902/jop.1984.55.6.325. [DOI] [PubMed] [Google Scholar]
  16. Ma J. K., Hunjan M., Smith R., Lehner T. Specificity of monoclonal antibodies in local passive immunization against Streptococcus mutans. Clin Exp Immunol. 1989 Sep;77(3):331–337. [PMC free article] [PubMed] [Google Scholar]
  17. 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. 1987 May;55(5):1274–1278. doi: 10.1128/iai.55.5.1274-1278.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Michalek S. M., Gregory R. L., Harmon C. C., Katz J., Richardson G. J., Hilton T., Filler S. J., McGhee J. R. Protection of gnotobiotic rats against dental caries by passive immunization with bovine milk antibodies to Streptococcus mutans. Infect Immun. 1987 Oct;55(10):2341–2347. doi: 10.1128/iai.55.10.2341-2347.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Okuda K., Kato T., Naito Y., Takazoe I., Kikuchi Y., Nakamura T., Kiyoshige T., Sasaki S. Protective efficacy of active and passive immunizations against experimental infection with Bacteroides gingivalis in ligated hamsters. J Dent Res. 1988 May;67(5):807–811. doi: 10.1177/00220345880670050201. [DOI] [PubMed] [Google Scholar]
  20. Persson G. R., Engel D., Whitney C., Darveau R., Weinberg A., Brunsvold M., Page R. C. Immunization against Porphyromonas gingivalis inhibits progression of experimental periodontitis in nonhuman primates. Infect Immun. 1994 Mar;62(3):1026–1031. doi: 10.1128/iai.62.3.1026-1031.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Prince A. M., Horowitz B., Brotman B. Sterilisation of hepatitis and HTLV-III viruses by exposure to tri(n-butyl)phosphate and sodium cholate. Lancet. 1986 Mar 29;1(8483):706–710. doi: 10.1016/s0140-6736(86)91101-3. [DOI] [PubMed] [Google Scholar]
  22. Sidi A. D., Ashley F. P. Influence of frequent sugar intakes on experimental gingivitis. J Periodontol. 1984 Jul;55(7):419–423. doi: 10.1902/jop.1984.55.7.419. [DOI] [PubMed] [Google Scholar]
  23. Van Winkelhoff A. J., Van der Velden U., Clement M., De Graaff J. Intra-oral distribution of black-pigmented Bacteroides species in periodontitis patients. Oral Microbiol Immunol. 1988 Jun;3(2):83–85. doi: 10.1111/j.1399-302x.1988.tb00087.x. [DOI] [PubMed] [Google Scholar]
  24. Zambon J. J., Reynolds H. S., Chen P., Genco R. J. Rapid identification of periodontal pathogens in subgingival dental plaque. Comparison of indirect immunofluorescence microscopy with bacterial culture for detection of Bacteroides gingivalis. J Periodontol. 1985 Nov;56(11 Suppl):32–40. doi: 10.1902/jop.1985.56.11s.32. [DOI] [PubMed] [Google Scholar]
  25. van Winkelhoff A. J., van Steenbergen T. J., de Graaff J. The role of black-pigmented Bacteroides in human oral infections. J Clin Periodontol. 1988 Mar;15(3):145–155. doi: 10.1111/j.1600-051x.1988.tb01561.x. [DOI] [PubMed] [Google Scholar]

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