Variation in the Bordetella pertussis Virulence Factors Pertussis Toxin and Pertactin in Vaccine Strains and Clinical Isolates in Finland

Abstract

There is evidence that pertussis is reemerging in vaccinated populations. We have proposed, and provided evidence for, one explanation for this phenomenon in The Netherlands: antigenic divergence between vaccine strains and circulating strains. Finland has a pertussis vaccination history very similar to that of The Netherlands, and yet there is no evidence for an increase in the incidence of pertussis to the extent that it was observed in The Netherlands. A comparison of the Bordetella pertussisstrains circulating in the two countries may shed light on the differences in pertussis epidemiology. Here we investigated whether temporal changes had occurred in pertussis toxin and pertactin types produced by the Finnish B. pertussis population. We show that strains isolated before 1964 produced the same pertussis toxin and pertactin variants as the vaccine strains. However, these vaccine types were replaced in later years, and in the 1990s most strains were distinct from the vaccine strains with respect to the two proteins. These trends are similar to those found in the Dutch B. pertussis population. An interesting difference between the contemporary Finnish and Dutch B. pertussis populations was found in the frequencies of pertactin variants, possibly explaining the distinct epidemiology of pertussis in the two countries.

Changes of the Swedish Bordetella pertussis population in incidence peaks during an acellular pertussis vaccine period between 1997 and 2004

“…For the prn gene, at least 10 alleles have been defined: prn1–9 and prn11 (11). They differ in the number of repeats (4–12) and composition of the repeat units (GGxxP) in Region 1 and Region 2. Based on non‐silent mutations, insertions or deletions, six different allelic types of the tracheal colonisation factor (tcfA) gene have been described, tcfA1–6 (11, 27).…”

“…Temporal changes in the Bordetella pertussis population were investigated first in the Netherlands, and later in the United States, Canada, Japan and many European countries, often showing an antigenic divergence between the vaccine strains and the circulating bacteria, particularly with respect to pertussis toxin and pertactin (5–15). Bacterial polymorphism and immune‐driven selection or adaptation have been suggested as important factors contributing to resurgence (7).…”

Genotypic Variation in the Bordetella pertussis Virulence Factors Pertactin and Pertussis Toxin in Historical and Recent Clinical Isolates in the United Kingdom

“…In addition, one pertactin type [prnA(4)] which had not been previously reported was seen at a frequency of 4 of 43 (9%) Finnish isolates from the 1990s (16,17). To explain the difference in the incidence of pertussis in The Netherlands and Finland, the authors of these studies postulated that pertussis WCVs containing only the pertactin type prnA(1) may confer differing levels of protection against strains of different prnA types [i.e., greater protection against prnA(2) strains predominating in Finland than against the prnA(3) strains predominating in The Netherlands] (16).…”

“…Similarly, the two pertussis toxin genotypes found in isolates from 1949 to 1954 were the same as those in the Dutch WCV: 8 of 14 (57%) were type ptxA (2), and 6 of 14 (43%) were type ptxA(3) (17), while in the period 1990 to 1996, only 2 of 15 (13%) isolates were of a Dutch WCV type, with the remaining 13 of 15 (87%) being ptxA(1) (17). A similar study on a small number of strains was also performed using isolates from Finland, where a resur-gence of pertussis has not been seen (16). The Finnish WCV, containing a single strain of B. pertussis [prnA(1) ptxA(3)], was introduced in 1962 and combined with an additional strain [prnA(1) ptxA (2)] in 1976.…”

“…Analysis of the Finnish isolates revealed a similar shift from all 5 isolates being of type prnA (1) in 1953 to 1964 (i.e., the same prnA type as found in the Finnish WCV) to only 3 of 43 (7%) isolates of the vaccine type [prnA (1)] from 1990 to 1996. There also appeared to have been a shift in circulating strains containing the toxin type found in the Finnish WCV, ptxA (2), from all 5 isolates in strains from 1953 to 1964 to 40 of 40 (100%) of type ptxA(1) (i.e., a non-Finnish WCV type) from 1990 to 1996 (16). Significant differences were seen between the two countries in the proportion of isolates of pertactin gene types prnA (2) and prnA (3).…”