Skip to main content
    • Aa
    • Aa

Pertussis resurgence: waning immunity and pathogen adaptation – two sides of the same coin

  • F. R. MOOI (a1), N. A. T. VAN DER MAAS (a2) and H. E. De MELKER (a2)

Pertussis or whooping cough has persisted and resurged in the face of vaccination and has become one of the most prevalent vaccine-preventable diseases in Western countries. The high circulation rate of Bordetella pertussis poses a threat to infants that have not been (completely) vaccinated and for whom pertussis is a severe, life-threatening, disease. The increase in pertussis is mainly found in age groups in which immunity has waned and this has resulted in the perception that waning immunity is the main or exclusive cause for the resurgence of pertussis. However, significant changes in B. pertussis populations have been observed after the introduction of vaccinations, suggesting a role for pathogen adaptation in the persistence and resurgence of pertussis. These changes include antigenic divergence with vaccine strains and increased production of pertussis toxin. Antigenic divergence will affect both memory recall and the efficacy of antibodies, while higher levels of pertussis toxin may increase suppression of the innate and acquired immune system. We propose these adaptations of B. pertussis have decreased the period in which pertussis vaccines are effective and thus enhanced the waning of immunity. We plead for a more integrated approach to the pertussis problem which includes the characteristics of the vaccines, the B. pertussis populations and the interaction between the two.

Corresponding author
* Author for correspondence: Professor F. R. Mooi, Laboratory for Infectious Disease, Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. (Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1. JI Ward , Bordetella pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized Acellular Pertussis Vaccine Trial (APERT). Clinical Infectious Diseases 2006; 43: 151157.

2. P Rendi-Wagner , The seroepidemiology of Bordetella pertussis in Israel – estimate of incidence of infection. Vaccine 2010; 28: 32853290.

3. SC de Greeff , Seroprevalence of pertussis in the Netherlands: evidence for increased circulation of Bordetella pertussis PLoS One 2010; 5: e14183.

4. HO Hallander , Seroprevalence of pertussis antitoxin (anti-PT) in Sweden before and 10 years after the introduction of a universal childhood pertussis vaccination program. Acta Pathologica, Microbiologica, et Immunologica Scandinavica 2009; 117: 912922.

5. SC de Greeff , Pertussis disease burden in the household: how to protect young infants. Clinical Infectious Diseases 2010; 50: 13391345.

6. AM Wendelboe , Duration of immunity against pertussis after natural infection or vaccination. Pediatric Infectious Diseases Journal 2005; 24 (5 Suppl.): S58S61.

8. JS Lavine , Short-lived immunity against pertussis, age-specific routes of transmission, and the utility of a teenage booster vaccine. Vaccine 2012; 30: 544551.

9. NP Klein , Waning protection after fifth dose of acellular pertussis vaccine in children. New England Journal of Medicine 2012; 367: 10121019.

10. MA Witt , PH Katz , DJ Witt . Unexpectedly limited durability of immunity following acellular pertussis vaccination in pre-adolescents in a North American outbreak. Clinical Infectious Diseases 2012; 54: 17301735.

11. L Gustafsson , Long-term follow-up of Swedish children vaccinated with acellular pertussis vaccines at 3, 5, and 12 months of age indicates the need for a booster dose at 5 to 7 years of age. Pediatrics 2006; 118: 978984.

13. D de Gouw , Pertussis: a matter of immune modulation. FEMS Microbiology Reviews 2011; 35: 441474.

16. JS Lavine , AA King , ON Bjornstad . Natural immune boosting in pertussis dynamics and the potential for long-term vaccine failure. Proceedings of the National Academy of Sciences USA 2011; 108: 72597264.

19. FR Mooi . Bordetella pertussis and vaccination: the persistence of a genetically monomorphic pathogen. Infection, Genetics and Evolution 2010; 10: 3649.

20. Q He , J Mertsola . Factors contributing to pertussis resurgence. Future Microbiology 2008; 3: 329339.

21. LM Schouls , Multiple-locus variable-number tandem repeat analysis of Dutch Bordetella pertussis strains reveals rapid genetic changes with clonal expansion during the late 1990s. Journal of Bacteriology 2004; 186: 54965505.

22. FR Mooi , Bordetella pertussis strains with increased toxin production associated with pertussis resurgence. Emerging Infectious Diseases 2009; 15: 12061213.

23. S Octavia , Insight into evolution of Bordetella pertussis from comparative genomic analysis: evidence of vaccine-driven selection. Molecular Biology and Evolution 2011; 28: 707715.

24. MJ Bart , Comparative genomics of prevaccination and modern Bordetella pertussis strains. BMC Genomics 2010; 11: 627.

25. M van Gent , Small mutations in Bordetella pertussis are associated with selective sweeps. PLoS One 2012; 7: e46407.

26. GA Berbers , SC de Greeff , FR Mooi . Improving pertussis vaccination. Human Vaccines 2009; 5: 497503.

29. J Storsaeter , Levels of anti-pertussis antibodies related to protection after household exposure to Bordetella pertussis. Vaccine 1998; 16: 19071916.

30. H Kuno-Sakai , M Kimura , H Watanabe . Verification of components of acellular pertussis vaccines that have been distributed solely, been in routine use for the last two decades and contributed greatly to control of pertussis in Japan. Biologicals 2004; 32: 2935.

31. MT De Magistris , Human T cell clones define S1 subunit as the most immunogenic moiety of pertussis toxin and determine its epitope map. Journal of Experimental Medicine 1989; 169: 15191532.

32. B Trollfors , A placebo-controlled trial of a pertussis-toxoid vaccine. New England Journal of Medicine 1995; 333: 10451050.

34. L Zhang , Acellular vaccines for preventing whooping cough in children. Cochrane Database of Systematic Reviews 2011. Issue 1. Art. No. CD001478.

36. A Advani , Appearance of Fim3 and ptxP3-Bordetella pertussis strains, in two regions of Sweden with different vaccination programs. Vaccine 2011; 29: 34383442.

37. T Kallonen , Rapid detection of the recently emerged Bordetella pertussis strains with the ptxP3 pertussis toxin promoter allele by real-time PCR. Clinical Microbiology and Infection 2012; 18: E377379.

39. RF Petersen , Temporal trends in Bordetella pertussis populations, Denmark, 1949–2010. Emerging Infectious Diseases 2012; 18: 767774.

40. AJ Schmidtke , Population diversity among Bordetella pertussis isolates, United States, 1935–2009. Emerging Infectious Diseases 2012; 18: 12481255.

42. LC Madoff , Group B streptococci escape host immunity by deletion of tandem repeat elements of the alpha C protein. Proceedings of the National Academy of Sciences USA 1996; 93: 41314136.

45. NH Carbonetti . Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools. Future Microbiology 2010; 5: 455469.

46. C Pierce , N Klein , M Peters . Is leukocytosis a predictor of mortality in severe pertussis infection? Intensive Care Medicine 2000; 26: 15121514.

47. A Advani , Clinical outcome of pertussis in Sweden: association with pulsed-field gel electrophoresis profiles and serotype. Acta Pathologica, Microbiologica et Immunologica Scandinavica 2007; 115: 736742.

49. V Bouchez , Bordetella parapertussis isolates not expressing pertactin circulating in France. Clinical Microbiology and Infection 2011; 17: 675682.

51. AM Barkoff , Appearance of Bordetella pertussis strains not expressing the vaccine antigen pertactin in Finland. Clinical and Vaccine Immunology 2012; 19: 17031704.

52. AJ King , Role of the polymorphic region 1 of the Bordetella pertussis protein pertactin in immunity. Microbiology 2001; 147: 28852895.

54. D Bottero , Pulse field gel electrophoresis, pertactin, pertussis toxin S1 subunit polymorphisms and surfaceome analysis of vaccine and clinical Bordetella pertussis strains. Clinical Vaccine Immunology 2007; 14: 14901498.

55. E Komatsu , Synergic effect of genotype changes in pertussis toxin and pertactin on adaptation to an acellular pertussis vaccine in the murine intranasal challenge model. Clinical Vaccine Immunology 2010; 17: 807812.

56. M van Gent , Studies on prn variation in the mouse model and comparison with epidemiological data. PLoS One 2011; 6: e18014.

59. D Greco , A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. Progetto Pertosse Working Group. New England Journal of Medicine 1996; 334: 341348.

60. FR Mooi , SC de Greeff . The case for maternal vaccination against pertussis. Lancet Infectious Diseases 2007; 7: 614624.

61. SC de Greeff , Estimation of pertussis household transmission rates and the impact of cocooning vaccination strategies on infant pertussis. Epidemiology 2012; 23: 852860.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Epidemiology & Infection
  • ISSN: 0950-2688
  • EISSN: 1469-4409
  • URL: /core/journals/epidemiology-and-infection
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 13
Total number of PDF views: 132 *
Loading metrics...

Abstract views

Total abstract views: 1134 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 27th July 2017. This data will be updated every 24 hours.