Bordetella pertussis and pertactin-deficient clinical isolates: lessons for pertussis vaccines

Abstract

Bordetella pertussis causes whooping cough in humans, a highly transmissible respiratory disease life threatening for unvaccinated infants. Vaccination strategies were thus introduced worldwide with great success in developed countries reaching high vaccine coverage with efficacious vaccines. In the late 20th/early 21st century, acellular pertussis vaccines replaced whole cell pertussis vaccines but B. pertussis still circulates and evolves in humans, its only known reservoir. The latest transformation of this pathogen, and of its close relative Bordetella parapertussis, is the loss of pertactin production, a virulence factor included in different acellular pertussis vaccines. The real impact of this evolution on acellular pertussis vaccines efficacy and effectiveness should be assessed through standardized surveillance and isolation of B. pertussis and B. parapertussis worldwide.

Keywords::

• acellular vaccine
• autotransporter
• bacterial evolution
• Bordetella pertussis
• pertactin
• vaccine selection

Financial & competing interests disclosure

This work has been supported by Institut Pasteur and Centre National de la Recherche Scientifique (CNRS). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Bordetella pertussis is a gram-negative bacterium responsible for pertussis or whooping cough, a severe respiratory disease presenting characteristic cycles linked to increase in the proportion of humans susceptible to infection and to small changes in the bacterial population.

• B. pertussis has been targeted by vaccine-induced selective pressure since the 1940s–1950s in developed countries with first the use of whole cell pertussis vaccines containing whole killed bacteria and then the use of acellular pertussis vaccines introduced during the 1990s targeting pertussis toxin and 1–4 secreted or membrane adhesins produced by B. pertussis.

• Whole cell pertussis vaccines controlled circulating isolates similar to vaccine strains as evidence by antigenic drifts and changes at the genomic level, but in the decades following acellular pertussis vaccine introduction, several countries reported the emergence of isolates lacking the production of one acellular pertussis vaccine antigen, pertactin (PRN), which is an adhesin remaining at the bacterial surface.

• Although highly probable, the direct relation between acellular pertussis vaccine introduction and increase in B. pertussis PRN-deficient isolate prevalence is still speculative. Since B. parapertussis isolates presenting the same phenotype are also collected while this species should not be impacted by pertussis vaccine-induced immunity, this phenotype might as well be a transient evolution of these species or an ongoing adaptation to the human host.

• The lack of PRN production does not impact the virulence or transmission of B. pertussis and the possible impact of this phenotype on acellular pertussis vaccine effectiveness and/or efficacy needs to be assessed by future studies in the human population.

• Evolution of bacterial populations under vaccine pressure is multifactorial and the type of vaccine used, the vaccine schedule as well as the vaccine coverage needs to be accounted for when analyzing these changes.

• Pertussis vaccination strategies are at a turning point and development of future vaccines is currently debated, but no scientific consensus has been reached for the moment on what path to follow and how vaccines should evolve.

• The recent advances in high-throughput sequencing and proteomics as well as the use of different animal models should help the scientific community better understand the pathophysiology of pertussis and the involvement of cellular immunity in control of B. pertussis infections.

• Establishing worldwide reference laboratories, harmonizing epidemiological studies and collecting B. pertussis isolates should be a priority to better understand the impact of vaccination on B. pertussis populations or the role of Bordetella species evolution on pertussis vaccines effectiveness.