Pertactin-DeficientBordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis

Abstract

B ordetella pertussis, the causative agent of pertussis (whooping cough), continues to reemerge in countries that have high vaccine coverage, such as the United States, and has accelerated since the switch during the mid-1990s from whole-cell pertussis (wP) formulations comprising many partially characterized bacterial proteins to the less reactogenic 1-5 component acellular pertussis (aP) vaccines (1,2). These aP vaccines, including DTaP (diphtheria, tetanus, and aP for children) and Tdap (tetanus, diphtheria, and aP for adolescents and adults), protect against disease, but this protection wanes rapidly and does not prevent colonization or transmission of the pathogen (3-5). In this background of suboptimally performing aP vaccines, many countries have noted the emergence and expansion of strains specifi cally lacking pertactin (PRN), a membrane bound autotransporter, and 1 of up to 5 B. pertussis protein antigens included in the vaccines (6-11).

Evolution of Bordetella pertussis over a 23-year period in France, 1996 to 2018

“…Several genetic events leading to PRN expression loss have been reported from different studies [ 5 , 27 , 28 ]. Here, we observed two main genomic events (IS 481 insertion or a large inversion) that led to impairment of PRN production, in agreement with observations in other world regions [ 7 , 27 , 29 ]. This pattern reflects convergent evolution and is further evidence that loss of expression of PRN is under strong selective pressure [ 30 ].…”

Bbvac: A Live Vaccine Candidate That Provides Long-Lasting Anamnestic and Th17-Mediated Immunity against the Three Classical Bordetella spp.

“…Current acellular vaccines are very safe and efficient in preventing severe symptoms of disease but are not able to prevent colonization of the nasal cavity and subsequent transmission to new hosts ( 7 , 8 ). In addition, the immunity they produce wanes relatively rapidly ( 9 – 11 ), and there is growing evidence of vaccine-driven evolution of key vaccine antigens, leading to fears of even larger outbreaks ( 12 – 14 ). In 2014, the number of cases of whooping cough was estimated to be over 24 million worldwide ( 15 ), underscoring the imperative need for new and improved vaccines.…”

Genomic library of Bordetella

“…The population of Bp has been noted to evolve in response to the selective pressure exerted by vaccination, in particular in countries using the acellular vaccines [23,59]. The proposed vaccine schemes will help keeping track of the circulating strains and defining the prevalence of particular sublineages, including those that are deficient for pertactin production [27,60,61].…”

“…In most countries using acellular vaccines, isolates characterized by ptxP3 and either fim3-1 or fim3-2 alleles are currently largely predominant, whereas isolates of the ancestral ptxP1 genotype still predominate elsewhere, for example in China [24,26]. In addition, in countries that use acellular vaccines, an increasing proportion of Bp isolates are deficient for the production of the immunodominant surface protein pertactin, raising questions on future vaccine effectiveness [27]. The nomenclature of genotypic markers, sublineages and strain subtypes needs unification to facilitate collective studies of the global epidemiology and population dynamics in Bp.…”