Polymorphism of Bordetella pertussis Isolates Circulating for the Last 10 Years in France, Where a Single Effective Whole-Cell Vaccine Has Been Used for More than 30 Years

Abstract

We compared Bordetella pertussis isolates collected in France over the last 10 years, the vaccine strains used for more than 30 years, and isolates collected before the introduction of generalized vaccination. The analysis included serotyping, pulsed-field gel electrophoresis of chromosomal DNA after digestion with XbaI and SpeI, and sequencing of the pt S1 gene, encoding the S1 subunit of pertussis toxin, and the prn gene, encoding the adhesin pertactin. We found that the incidence of infection increases every 3 years. Ninety-five per cent of the isolates analyzed express type 3 fimbriae. Most of the isolates circulating since 1991, unlike the vaccinal strains, express a type A pertussis toxin and a type 2 pertactin. The isolates could be classified into five major groups by pulsed-field gel electrophoresis. Most of these groups correlated with the pertactin type expressed by the isolates. Pulsed-field gel electrophoresis is more discriminative than sequencing particular genes since it could differentiate isolates expressing type 2 pertactin into two subgroups: those circulating in 1993 to 1997 and those circulating in 1997 to 2001. This observation suggests that there has been continuous evolution of the B. pertussis population.

Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

“…Besides vaccine-driven evolution of B. pertussis populations (Octavia et al, 2011), epidemic lineages circulate (Advani et al, 2009;Weber et al, 2001) and need to be considered as well since they are possibly responsible for the characteristic cycles of pertussis, as they might present a particular phenotype and/or fitness. The result obtained with anti-FHA antiserum might reflect such a population of B. pertussis, as FR5133 and FR5187 were collected during the same pertussis cycle and are closely related, as evidenced by their segregation in a neighbour-joining tree built from the concatenated sequences of their SNPs obtained against B.…”

“…Specific polyclonal mouse antisera directed against AC-Hly, PT, FHA and PRN were obtained as described by Weber et al (2001). Briefly, 4-week-old BALB/c mice were immunized subcutaneously four times at 4 week intervals with 10 mg of each purified antigen adsorbed onto aluminium hydroxide and were bled 7 days after the last injection.…”

“…Clinical isolates were tested for virulence factor production by Western blot using the mouse polyclonal antisera obtained after immunizing mice with purified antigens as described above and by Weber et al (2001).…”

“…To protect this population from the disease, whole-cell pertussis vaccine (WPV) was introduced in 1959 in France for primary and booster immunization of children. This strategy managed to control circulating isolates similar to WPV strains, and dramatically decreased the morbidity and mortality of the disease in this age group (Baron et al, 1998;Bonmarin et al, 2007;Bouchez et al, 2008;Caro et al, 2005Caro et al, , 2006Weber et al, 2001). In 1998, acellular pertussis vaccines (APVs) were introduced for adolescent booster vaccination (Institut de Veille Sanitaire, 1998) and afterwards replaced WPV for child immunization as well.…”

Efficacy and effectiveness of acellular pertussis vaccines: a 20-year Swedish experience

“…There is documented evidence from many countries, including Sweden, that circulating variants of B. pertussis are essentially different from those strains used for vaccine production. The results of strain characterization by means of pulsed-field gel electrophoresis, serotype, toxin and PRN types indicate that there have been genetic shifts in the B. pertussis population over the years [14][15][16][17]. Some clones have been widely spread and also appear to be more aggressive than others [15,18,19].…”