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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)
  • DOI:
  • Published online: 13 February 2013

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:
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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. JIWard , 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. HOHallander , 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.

7.HJ Wearing , P Rohani . Estimating the duration of pertussis immunity using epidemiological signatures. PLoS Pathogens 2009; 5: e1000647.

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.

12. SLSheridan , Number and order of whole cell pertussis vaccines in infancy and disease protection. Journal American Medical Association 2012; 308: 454456.

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

14.RJ Vandebriel , Association of Bordetella pertussis with host immune cells in the mouse lung. Microbial Pathogenesis 2003; 35: 1929.

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.

17.FR Mooi , Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in The Netherlands: temporal trends and evidence for vaccine-driven evolution. Infection and Immunity 1998; 66: 670675.

18.FR Mooi , IH van Loo , AJ King . Adaptation of Bordetella pertussis to vaccination: a cause for its reemergence? Emerging Infectious Diseases 2001; 7 (3 Suppl.): 526528.

19. FRMooi . 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. SOctavia , 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.

28.Anon. Vaccination against whooping-cough; relation between protection in children and results of laboratory tests; a report to the Whooping-cough Immunization Committee of the Medical Research Council and to the medical officers of health for Cardiff, Leeds, Leyton, Manchester, Middlesex, Oxford, Poole, Tottenham, Walthamstow, and Wembley. British Medical Journal 1956; 2: 454462.

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.

33.A Hviid , Impact of routine vaccination with a pertussis toxoid vaccine in Denmark. Vaccine 2004; 22: 35303534.

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

35.DJ Litt , SE Neal , NK Fry . Changes in genetic diversity of the UK Bordetella pertussis population between 1920 and 2006 reflect vaccination coverage and the emergence of a single dominant clonal type. Journal Clinical Microbiology 2009; 47: 680688.

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.

38.S Octavia , Newly emerging clones of Bordetella pertussis carrying prn2 and ptxP3 alleles implicated in Australian pertussis epidemic in 2008–2010. Journal of Infectious Diseases 2012; 205: 12201224.

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.

41.JD Cherry , A search for serologic correlates of immunity to Bordetella pertussis cough illnesses. Vaccine 1998; 16: 19011906.

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.

43.M van Gent , SNP-based typing: a useful tool to study Bordetella pertussis populations. PLoS One 2011; 6: e20340.

44.T Bedford , S Cobey , M Pascual . Strength and tempo of selection revealed in viral gene genealogies. BMC Evolutionary Biology 2011; 11: 220.

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.

48.KM Edwards , Comparison of 13 acellular pertussis vaccines: overview and serologic response. Pediatrics 1995; 96: 548557.

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

50.N Otsuka , Prevalence and genetic characterization of pertactin-deficient Bordetella pertussis in Japan. PLoS One 2012; 7: e31985.

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.

53.A Gzyl , Sequence variation in pertussis S1 subunit toxin and pertussis genes in Bordetella pertussis strains used for the whole-cell pertussis vaccine produced in Poland since 1960: efficiency of the DTwP vaccine-induced immunity against currently circulating B. pertussis isolates. Vaccine 2004; 22: 21222128.

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.

57.E Leininger , Comparative roles of the Arg-Gly-Asp sequence present in the Bordetella pertussis adhesins pertactin and filamentous hemagglutinin. Infection & Immunity 1992; 60: 23802385.

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.

62. CDC. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged <12 months – Advisory Committee on Immunization Practices (ACIP), 2011. Morbidity and Mortalilty Weekly Report 2011; 60: 14241426.

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