In several countries pertussis is re-emerging, despite a high vaccination coverage. It is suggested that antigenic divergence between vaccine strains and circulating strains, in particular with respect to pertactin, has contributed to pertussis re-emergence. Polymorphism in pertactin is essentially limited to region 1, which is composed of repeats and is located adjacent to an Arg-Gly-Asp motif implicated in adherence. Evidence is provided for the immunological relevance of polymorphism in region 1. Region 1 was found to contain a B-cell epitope recognized in both humans and mice. Furthermore, variation in region 1 affected antibody binding and, in a mouse respiratory infection model, the efficacy of a whole-cell vaccine. Moreover, passive and active immunization indicated that region 1 confers protective immunity. An mAb directed against a linear conserved epitope conferred cross-immunity against isolates with distinct pertactin variants. The results indicate an important role of region 1 of pertactin in immunity.


Article metrics loading...

Loading full text...

Full text loading...



  1. Andrews, R., Herceg, A. & Roberts, C. (1997). Pertussis notifications in Australia, 1991 to 1997. Commun Dis Intell 21, 145-148. [Google Scholar]
  2. Bass, J. W. & Stephenson, S. R. (1987). The return of pertussis. Pediatr Infect Dis J 6, 141-144.[CrossRef] [Google Scholar]
  3. Bass, J. W. & Wittler, R. R. (1994). Return of epidemic pertussis in the United States. Pediatr Infect Dis J 13, 343-345.[CrossRef] [Google Scholar]
  4. Berbers, G. A. M., Marzec, A. H. J. O., Bastmeijer, M., Gageldonk, P. M. & Plantinga, A. D. (1993). Blocking ELISA for detection of mumps virus antibodies in human sera. J Virol Methods 42, 155-168.[CrossRef] [Google Scholar]
  5. Boursaux-Eude, C., Thiberge, S., Carletti, G. & Guiso, N. (1999). Intranasal murine model of Bordetella pertussis infection: II. Sequence variation and protection induced by a tricomponent acellular vaccine. Vaccine 17, 2651-2660.[CrossRef] [Google Scholar]
  6. Brugghe, H. F., Timmermans, H. A. M., Van Unen, L. M. A., Ten Hove, G. J., Van de Werken, G., Poolman, J. T. & Hoogerhout, P. (1994). Simultaneous multiple synthesis and selective conjugation of cyclized peptides, derived from a surface-loop of a meningococcal class I outer membrane protein. Int J Pept Protein Res 43, 166-172. [Google Scholar]
  7. Charles, I. G., Li, J. L., Roberts, M. & 13 other authors (1991). Identification and characterization of a protective immunodominant B cell epitope of pertactin (P.69) from Bordetella pertussis. Eur J Immunol 21, 1147–1153.[CrossRef] [Google Scholar]
  8. Charles, I., Fairweather, N., Pickard, D., Beesley, J., Anderson, R., Dougan, G. & Roberts, M. (1994). Expression of the Bordetella pertussis P.69 pertactin adhesin in Escherichia coli: fate of the carboxy-terminal domain. Microbiology 140, 3301-3308.[CrossRef] [Google Scholar]
  9. Cherry, J. D. & Olin, P. D. (1999). The sciences and fiction of pertussis vaccines. Pediatrics 104, 1381-1384.[CrossRef] [Google Scholar]
  10. Cherry, J. D., Gornbein, J., Heininger, U. & Stehr, K. (1998). A search for serologic correlates of immunity to Bordetella pertussis cough illnesses. Vaccine 16, 1901-1906.[CrossRef] [Google Scholar]
  11. DeSerres, G., Boulianne, N., Douville-Fradet, M. & Duval, B. (1995). Pertussis in Quebec: ongoing epidemic since the late 1980s. Can Commun Dis Rep 15, 45-48. [Google Scholar]
  12. Drijfhout, J. W., Bloemhoff, W., Poolman, J. T. & Hoogerhout, P. (1990). Solid-phase synthesis and applications of N-(S-acetylmercaptoacetyl) peptides. Anal Biochem 187, 349-354.[CrossRef] [Google Scholar]
  13. Emsley, P., Charles, I. G., Fairweather, N. F. & Isaacs, N. W. (1996). Structure of Bordetella pertussis virulence factor P.69 pertactin. Nature 381, 90-92.[CrossRef] [Google Scholar]
  14. Everest, P., Li, J. L., Douce, G., Charles, I., Deazavedo, J., Chatfield, S., Dougan, G. & Roberts, M. (1996). Role of the Bordetella pertussis P.69/pertactin protein and the P.69/pertactin RGD motif in the adherence to and invasion of mammalian cells. Microbiology 142, 3261-3268.[CrossRef] [Google Scholar]
  15. Guiso, N., Capiau, C., Carletti, G., Poolman, J. & Hauser, P. (1999). Intranasal murine model of Bordetella pertussis infection. I. Prediction of protection in human infants by acellular vaccines. Vaccine 17, 2366-2376.[CrossRef] [Google Scholar]
  16. Henderson, I. R., Navarro-Garcia, F. & Nataro, J. P. (1998). The great escape: structure and function of the autotransporter proteins. Trends Microbiol 6, 370-378.[CrossRef] [Google Scholar]
  17. Hewlett, E. L. (1997). Pertussis: current concepts of pathogenesis and prevention. Pediatr Infect Dis J 16, S78-S84.[CrossRef] [Google Scholar]
  18. Kimura, A., Mountzouros, K. T., Relman, D. A., Falkow, S. & Cowell, J. L. (1990).Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model. Infect Immun 58, 7-16. [Google Scholar]
  19. Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.[CrossRef] [Google Scholar]
  20. Leininger, E., Roberts, M., Kenimer, J. G., Charles, I. G., Fairweather, N., Novotny, P. & Brennan, M. J. (1991). Pertactin, an Arg Gly Asp containing Bordetella pertussis surface protein that promotes adherence of mammalian cells. Proc Natl Acad Sci USA 88, 345-349.[CrossRef] [Google Scholar]
  21. Leininger, E., Ewanowich, C. A., Bhargava, A., Peppler, M. S., Kenimer, J. G. & Brennan, M. J. (1992). Comparative roles of the Arg Gly Asp sequence present in the Bordetella pertussis adhesins pertactin and filamentous hemagglutinin. Infect Immun 60, 2380-2385. [Google Scholar]
  22. Li, L. J., Dougan, G., Novotny, P. & Charles, I. G. (1991). P.70 pertactin, an outer-membrane protein from Bordetella parapertussis: cloning, nucleotide sequence and surface expression in Escherichia coli. Mol Microbiol 5, 409-417.[CrossRef] [Google Scholar]
  23. van Loo, I. H., Van der Heide, H. G., Nagelkerke, N. J., Verhoef, J. & Mooi, F. R. (1999). Temporal trends in the population structure of Bordetella pertussis during 1949–1996 in a highly vaccinated population. J Infect Dis 179, 915-923.[CrossRef] [Google Scholar]
  24. Mastrantonio, P., Spigaglia, P., Van Oirschot, H., Van der Heide, H., Heuvelman, K., Stefanelli, P. & Mooi, F. R. (1999). Antigenic variants in Bordetella pertussis strains isolated from vaccinated and unvaccinated children. Microbiology 145, 2069-2075.[CrossRef] [Google Scholar]
  25. de Melker, H. E., Conyn-van Spaendonck, M. A., Rumke, H. C., van Wijngaarden, J. K., Mooi, F. R. & Schellekens, J. F. (1997). Pertussis in The Netherlands: an outbreak despite high levels of immunization with whole-cell vaccine. Emerg Infect Dis 3, 175-178.[CrossRef] [Google Scholar]
  26. Mills, K. H., Ryan, M., Ryan, E. & Mahon, B. P. (1998). A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis. Infect Immun 66, 594-602. [Google Scholar]
  27. Mooi, F. R., Van Oirschot, H., Heuvelman, K., Van der Heide, H. G. J., Gaastra, W. & Willems, R. J. L. (1998). Polymorphism in the Bordetella pertussis virulence factors P.69/Pertactin and pertussis toxin in the Netherlands: temporal trends and evidence for vaccine-driven evolution. Infect Immun 66, 670-675. [Google Scholar]
  28. Mooi, F. R., He, Q., Van Oirschot, H. & Mertsola, J. (1999). Variation in Bordetella pertussis virulence factors pertussis toxin and pertactin in vaccine strains and clinical isolates in Finland. Infect Immun 67, 3133-3134. [Google Scholar]
  29. Novotny, P., Chubb, A. P., Cownley, K. & Charles, I. G. (1991). Biologic and protective properties of the 69 kDA outer membrane protein of Bordetella pertussis: a novel formulation for an acellular pertussis vaccine. J Infect Dis 164, 114-122.[CrossRef] [Google Scholar]
  30. Plotkin, S. A. & Cadoz, M. (1997). Acellular vaccine efficacy trials. Pediatr Infect Dis J 16, 913-914.[CrossRef] [Google Scholar]
  31. Ravetch, J. V. & Clynes, R. A. (1998). Divergent roles for Fc receptors and complement in vivo. Annu Rev Immunol 16, 421-432.[CrossRef] [Google Scholar]
  32. Roberts, M., Fairweather, N. F., Leininger, E., Pickard, D., Hewlett, E. L., Robinson, A., Hayward, C., Dougan, G. & Charles, I. G. (1991). Construction and characterization of Bordetella pertussis mutants lacking the vir regulated P.69 outer membrane protein. Mol Microbiol 5, 1393-1404.[CrossRef] [Google Scholar]
  33. Robinson, A., Ashworth, L. A., Baskerville, A. & Irons, L. I. (1985). Protection against intranasal infection of mice with Bordetella pertussis. Dev Biol Stand 61, 165-172. [Google Scholar]
  34. Rouppe van der Voort, E. M., Kuipers, B., Brugghe, H. F., Van Unen, L. M., Timmermans, H. A., Hoogerhout, P. & Poolman, J. T. (1997). Epitope specificity of murine and human bactericidal antibodies against PorA P1.7,16 induced with experimental meningococcal group B vaccines. FEMS Immunol Med Microbiol 17, 139-148.[CrossRef] [Google Scholar]
  35. Sato, H. & Sato, Y. (1984).Bordetella pertussis infection in mice: correlation of specific antibodies against two antigens, pertussis toxin, and filamentous hemagglutinin with mouse protection in an intracerebral or aerosol challenge system. Infect Immun 46, 415-421. [Google Scholar]
  36. Shahin, R. D., Brennan, M. J., Li, Z. M., Meade, B. D. & Manclark, C. R. (1990). Characterization of the protective capacity and immunogenicity of the 69 kD outer membrane protein of Bordetella pertussis. J Exp Med 171, 63-73.[CrossRef] [Google Scholar]
  37. Storsaeter, J., Hallander, H. O., Gustafsson, L. & Olin, P. (1998). Levels of anti-pertussis antibodies related to protection after household exposure to Bordetella pertussis. Vaccine 16, 1907-1916.[CrossRef] [Google Scholar]
  38. Tam, J. & Zavala, F. (1989). Multiple Antigen Peptide. A novel approach to increase detection sensitivity of synthetic peptides in solid-phase immunoassays. J Immunol Methods 124, 53-61.[CrossRef] [Google Scholar]
  39. Van der Ley, P., Heckels, J. E., Virji, M., Hoogerhout, P. & Poolman, T. (1991). Topology of outer membrane porins in Neisseria spp. Infect Immun 59, 2963-2971. [Google Scholar]
  40. Verwey, W. F., Thiele, E. H., Sage, D. N. & Schuckhardt, L. T. (1949). A simplified liquid culture medium for the growth of Haemophilus pertussis. J Bacteriol 50, 127-134. [Google Scholar]
  41. Willems, R. J. L. & Mooi, F. R. (1996). From whole cell to acellular pertussis vaccines. Rev Med Microbiol 7, 13-21.[CrossRef] [Google Scholar]
  42. Zhang, J. M., Cowell, J. L., Steven, A. C. & Manclark, C. R. (1985). Purification of serotype 2 fimbriae of Bordetella pertussis and their identification as a mouse protective antigen. Dev Biol Stand 61, 173-185. [Google Scholar]

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error