Pertussis vaccine – under vaccine selection pressure? Resource page

Any cause that reduces reproductive success in a proportion of a population potentially exerts evolutionary pressure or selection pressure.With sufficient pressure, inherited traits that mitigate its effects—even if they would be deleterious in other circumstances—can become widely spread through a population – Wikipedia

A resurgence of pertussis or whooping cough has been observed in highly immunized populations. Studies have shown that there are other causes beyond increased awareness of disease, use of better diagnostic tools and improved surveillance methods. Waning vaccine-induced immunity (secondary failure) has been identified in many countries and antigenic divergence has been found between vaccine strains and clinical isolates in many countries with high vaccination coverage.

Here are the links to some studies that identify vaccine selection pressure / antigenic divergence as a cause for pertussis re emergence.

Adaptation of Bordetella pertussis to vaccination: a cause for its reemergence?

In the Netherlands, as in many other western countries, pertussis vaccines have been used extensively for more than 40 years. Therefore, it is conceivable that vaccine-induced immunity has affected the evolution of Bordetella pertussis. Consistent with this notion, pertussis has reemerged in the Netherlands, despite high vaccination coverage. Further, a notable change in the population structure of B. pertussis was observed in the Netherlands subsequent to the introduction of vaccination in the 1950s. Finally, we observed antigenic divergence between clinical isolates and vaccine strains, in particular with respect to the surface-associated proteins pertactin and pertussis toxin. Adaptation may have allowed B. pertussis to remain endemic despite widespread vaccination and may have contributed to the reemergence of pertussis in the Netherlands.

Antigenic Divergence between Bordetella pertussis Clinical Isolates from Moscow, Russia, and Vaccine Strains

Together with waning immunity, the antigenic divergence between vaccine strains and clinical isolates observed in the Moscow area may explain the persistence of pertussis, despite the high rates of vaccine coverage.

In the past few years, the pertussis epidemiological situation in Russia has been unfavorable. Regardless of the high rates of vaccination coverage for pertussis, we have registered an increase in the incidence of pertussis among school-aged children,  along  with  persistently  high  incidences  among  infants under 12 months of age. In addition, some cases of pertussis have been registered among vaccinated children (8, 23). Similar trends have been observed in many other countries (1, 2, 5, 6, 10). Researchers point to many reasons for the increased incidence of pertussis, including improved surveillance, waning immunity, and pathogen adaptation. The last possibility is supported by the fact that divergence in the protective antigens pertussis  toxin  (Ptx)  and  pertactin  (Prn)  has  been  observed between  vaccine  strains  and  the  strains  circulating  in  many countries

Bordetella pertussis isolates in Finland: serotype and fimbrial expression.

  1. pertussis continues  to  cause  epidemics  in  vaccinated populations  in  spite  of  high  vaccination  coverage.  As  a result  of  this  study  we  gained  more  information  of  the possible mechanisms the bacterium uses to infect highly vaccinated populations. This information is important for the future development of vaccines against pertussis.


Despite  extensive  vaccinations  in  Finland,  Fim2  strains were  the  most  common  serotype.  Fim3  strains  emerged since 1999 and the emergence coincided with nationwide epidemics. In a population with long-term vaccinations, Fim2 strains could express Fim3 during infection, showing a difference in fimbrial expression between in vivo and in vitro.

Global Population Structure and Evolution of Bordetella pertussis and Their Relationship with Vaccination.

Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production.

We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.

Changes in genetic diversity of the Bordetella pertussis population in the United Kingdom between 1920 and 2006 reflect vaccination coverage and emergence of a single dominant clonal type.

This supports a hypothesis that MLVA-27 is under some form of positive selection conferring increased survival in a highly vaccinated population.

Genomic analysis of isolates from the UK 2012 pertussis outbreak reveals that vaccine antigen genes are unusually fast evolving

Importantly, we demonstrate that acellular vaccine  antigen encoding genes are evolving at higher rates than other surface protein encoding genes. This was true even prior to the introduction of pertussis vaccines, but has become more pronounced since the introduction of the current acellular vaccines.

The fast evolution of vaccine antigen genes has serious consequences for the ability of current vaccines to continue to control pertussis.

Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in The Netherlands: temporal trends and evidence for vaccine-driven evolution.

These results suggest that vaccination has selected for strains which are antigenically distinct from vaccine strains.

There is evidence that the incidence of pertussis is increasing in populations vaccinated with WCVs (1, 4, 5, 11, 12), and our results suggest that one of the factors which has contributed to this phenomenon may be the decline of vaccine efficacy due to antigenic shifts in the B. pertussis population. Our findings also may have implications for the efficacy of ACVs, many of which contain  both  P.69  and  pertussis  toxin  (35).

Evolution of French Bordetella pertussis and Bordetella parapertussis isolates: increase of Bordetellae not expressing pertactin.

Hence, the generalized use of wP vaccine revealed polymorphisms within the B. pertussis population because it was not able to control all the circulating isolates [13]. The wP vaccine-induced herd immunity enabled isolates, as virulent as but different from the vaccine strains, to emerge [3].

In conclusion, even though genetic rearrangements took place in the absence of human interference [28], human vaccination strategies introduced a new challenge that bacterial populations had to overcome, promoting evolution and selection among these populations. It is clearly known now that in France, wP vaccination favoured genotypic changes (PFGE IV, ptxP3, prn2, ptxA1) in the B. pertussis population [6,7], changes which could not be observed in regions of low vaccine coverage (Senegal) [21]. Gene loss (RDs) and increase in insertion sequence elements are also part of the adaptation of the B. pertussis population to its host. Whether they are influenced by vaccination should be appreciated in regions with no or very low vaccine coverage. Continuous surveillance for antigenic change in B. pertussis and B. parapertussis strains is therefore required as a tool for monitoring pertussis vaccine effectiveness.

Pathogen adaptation under imperfect vaccination: implications for pertussis.

Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination.

This is exemplified by figure 1 (bottom panel),which shows the estimated incidence in vaccinated and unvaccinated children aged 5–9 years. This panel shows
that, although the incidence in unvaccinated children (ca 4% of the population) has increased considerably since 1995, the incidence in vaccinated children (ca 96% of the population) has increased much more strongly. As a result, the incidences in the vaccinated and unvaccinated cohorts are at present not significantly different.


One thought on “Pertussis vaccine – under vaccine selection pressure? Resource page

  1. Pingback: How to write a pro vaccine article | unavoidablyunsafe

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s