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. 1990 Oct;58(10):3369–3374. doi: 10.1128/iai.58.10.3369-3374.1990

Protective activities in mice of monoclonal antibodies against pertussis toxin.

H Sato 1, Y Sato 1
PMCID: PMC313662  PMID: 1698179

Abstract

Pertussis toxin (PT) protein, which is the most important protective antigen of Bordetella pertussis, has a hexameric structure composed of five subunits, designated S1 through S5. Immunoprotective activity of 20 different mouse monoclonal antibodies (MAbs) against pertussis toxin, 10 anti-S1, 1 anti-S2, 2 anti-S3, 4 anti-S23, and 3 anti-S4 antibodies, were investigated by aerosol and intracerebral challenges with virulent B. pertussis organisms in mice. Four anti-S1, named 1B7, 1D7, 3F11, and 10D6, and three anti-S23 antibodies, named 11E6, 10B5, and 10C9, showed the highest, and almost complete, protectivity against the aerosol challenge. Mouse protectivity against the intracerebral challenge was significant for these four anti-S1 MAbs but not for any of the three anti-S23 MAbs. Four anti-S1 and two anti-S4 MAbs did not protect the mice against either challenge. The other seven MAbs also showed dose-dependent moderate but significant protection against the aerosol challenge. In the aerosol challenge system, bacterial numbers and amounts of PT detected in the lung and the number of peripheral leukocytes were lower in the mice given the protective MAbs. All mice surviving 5 weeks after the infection produced high titers of antibodies against PT, filamentous hemagglutinin (FHA), and agglutinogens from the challenge organisms. A combination of the protective MAbs 1B7 and 11E6 strongly suppressed the disease and mortality of the mice at smaller amounts than with the anti-PT polyclonal antibody. Although combinations of one of the protective MAb and anti-FHA or anti-agglutinogen 2 also showed extremely high mouse protection without development of symptoms of the disease, antibody titers of the survivors against PT, FHA, and agglutinogens were significantly low. The foregoing results suggest that some important protective epitopes should be in S1 and S2 and/or S3, although there are both differences and similarities in the protective roles between anti-S1 and anti-S23 antibodies and also in the pathogenic mechanisms between aerosol and intracerebral infections. Furthermore, it was suggested that although not only FHA and agglutinogen 2 but also PT have roles as attachment factors, the processes of infection and protection are different between mice immunized with antibody against FHA or agglutinogen 2 and that against PT because the latter mice are also able to neutralize toxicity of PT diffused into the mice.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Hewlett E. L., Sauer K. T., Myers G. A., Cowell J. L., Guerrant R. L. Induction of a novel morphological response in Chinese hamster ovary cells by pertussis toxin. Infect Immun. 1983 Jun;40(3):1198–1203. doi: 10.1128/iai.40.3.1198-1203.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Imaizumi A., Suzuki Y., Ono S., Sato H., Sato Y. Heptakis(2,6-O-dimethyl)beta-cyclodextrin: a novel growth stimulant for Bordetella pertussis phase I. J Clin Microbiol. 1983 May;17(5):781–786. doi: 10.1128/jcm.17.5.781-786.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Kim K. J., Burnette W. N., Sublett R. D., Manclark C. R., Kenimer J. G. Epitopes on the S1 subunit of pertussis toxin recognized by monoclonal antibodies. Infect Immun. 1989 Mar;57(3):944–950. doi: 10.1128/iai.57.3.944-950.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Kimura A., Mountzouros K. T., Relman D. A., Falkow S., Cowell J. L. Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model. Infect Immun. 1990 Jan;58(1):7–16. doi: 10.1128/iai.58.1.7-16.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Lang A. B., Ganss M. T., Cryz S. J., Jr Monoclonal antibodies that define neutralizing epitopes of pertussis toxin: conformational dependence and epitope mapping. Infect Immun. 1989 Sep;57(9):2660–2665. doi: 10.1128/iai.57.9.2660-2665.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Munoz J. J., Arai H., Cole R. L. Mouse-protecting and histamine-sensitizing activities of pertussigen and fimbrial hemagglutinin from Bordetella pertussis. Infect Immun. 1981 Apr;32(1):243–250. doi: 10.1128/iai.32.1.243-250.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Oda M., Cowell J. L., Burstyn D. G., Manclark C. R. Protective activities of the filamentous hemagglutinin and the lymphocytosis-promoting factor of Bordetella pertussis in mice. J Infect Dis. 1984 Dec;150(6):823–833. doi: 10.1093/infdis/150.6.823. [DOI] [PubMed] [Google Scholar]
  8. Robinson A., Gorringe A. R., Funnell S. G., Fernandez M. Serospecific protection of mice against intranasal infection with Bordetella pertussis. Vaccine. 1989 Aug;7(4):321–324. doi: 10.1016/0264-410x(89)90193-x. [DOI] [PubMed] [Google Scholar]
  9. Robinson A., Irons L. I. Synergistic effect of Bordetella pertussis lymphocytosis-promoting factor on protective activities of isolated Bordetella antigens in mice. Infect Immun. 1983 May;40(2):523–528. doi: 10.1128/iai.40.2.523-528.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sato H., Ito A., Chiba J., Sato Y. Monoclonal antibody against pertussis toxin: effect on toxin activity and pertussis infections. Infect Immun. 1984 Nov;46(2):422–428. doi: 10.1128/iai.46.2.422-428.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sato H., Sato Y. Bordetella pertussis infection in mice: correlation of specific antibodies against two antigens, pertussis toxin, and filamentous hemagglutinin with mouse protectivity in an intracerebral or aerosol challenge system. Infect Immun. 1984 Nov;46(2):415–421. doi: 10.1128/iai.46.2.415-421.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sato H., Sato Y., Ito A. Monoclonal antibody against pertussis toxin: relationship between toxin neutralization and mouse protection activities. Ann Sclavo Collana Monogr. 1986;3(1-2):259–267. [PubMed] [Google Scholar]
  13. Sato H., Sato Y., Ito A., Ohishi I. Effect of monoclonal antibody to pertussis toxin on toxin activity. Infect Immun. 1987 Apr;55(4):909–915. doi: 10.1128/iai.55.4.909-915.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sato Y., Izumiya K., Sato H., Cowell J. L., Manclark C. R. Aerosol infection of mice with Bordetella pertussis. Infect Immun. 1980 Jul;29(1):261–266. doi: 10.1128/iai.29.1.261-266.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sato Y., Izumiya K., Sato H., Cowell J. L., Manclark C. R. Role of antibody to leukocytosis-promoting factor hemagglutinin and to filamentous hemagglutinin in immunity to pertussis. Infect Immun. 1981 Mar;31(3):1223–1231. doi: 10.1128/iai.31.3.1223-1231.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schou C., Au-Jensen M., Heron I. The interaction between pertussis toxin and 10 monoclonal antibodies. Acta Pathol Microbiol Immunol Scand C. 1987 Oct;95(5):177–187. doi: 10.1111/j.1699-0463.1987.tb00028.x. [DOI] [PubMed] [Google Scholar]
  17. Storsaeter J., Hallander H., Farrington C. P., Olin P., Möllby R., Miller E. Secondary analyses of the efficacy of two acellular pertussis vaccines evaluated in a Swedish phase III trial. Vaccine. 1990 Oct;8(5):457–461. doi: 10.1016/0264-410x(90)90246-i. [DOI] [PubMed] [Google Scholar]
  18. Tuomanen E., Weiss A. Characterization of two adhesins of Bordetella pertussis for human ciliated respiratory-epithelial cells. J Infect Dis. 1985 Jul;152(1):118–125. doi: 10.1093/infdis/152.1.118. [DOI] [PubMed] [Google Scholar]
  19. Yamakawa Y., Sato H., Sato Y. Isolation of pertussis toxin subunit proteins by reverse-phase high-performance liquid chromatography and reconstitution of the holotoxin molecule. Anal Biochem. 1990 Feb 15;185(1):176–181. doi: 10.1016/0003-2697(90)90276-f. [DOI] [PubMed] [Google Scholar]

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