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Infect Immun, February 1998, p. 670-675, Vol. 66, No. 2
Research Laboratory for Infectious Diseases,
Received 2 October 1997/Returned for modification 30 October
1997/Accepted 20 November 1997
The Bordetella pertussis proteins P.69 (also designated
pertactin) and pertussis toxin are important virulence factors and have
been shown to confer protective immunity in animals and humans. Both
proteins are used in the new generation of acellular pertussis vaccines
(ACVs), and it is therefore important to study the degree of antigenic
variation in these proteins. Sequence analysis of the genes for P.69
and the pertussis toxin S1 subunit, using strains collected from Dutch
patients in the period 1949 to 1996, revealed three P.69 and three S1
variants which show differences in amino acid sequence. Polymorphism in
P.69 was confined to a region comprised of repeats and located proximal
to the RGD motif involved in adherence to host tissues. Variation in S1
was observed in two regions previously identified as T-cell epitopes.
P.69 and S1 variants, identical to those included in the Dutch
whole-cell pertussis vaccine (WCV), were found in 100% of the strains
from the 1950s, the period when the WCV was introduced in The
Netherlands. However, nonvaccine types of P.69 and S1 gradually
replaced the vaccine types in later years and were found in ~90%
strains from 1990 to 1996. These results suggest that vaccination has
selected for strains which are antigenically distinct from vaccine
strains. Analysis of strains from vaccinated and nonvaccinated
individuals indicated that the WCV protects better against strains with
the vaccine type P.69 than against strains with non-vaccine types
(P = 0.024). ACVs contain P.69 and S1 types which are
found in only 10% of recent Dutch B. pertussis isolates,
implying that they do not have an optimal composition. Our findings
cast a new light on the reemergence of pertussis in highly vaccinated
populations and may have major implications for the long-term efficacy
of both WCVs and ACVs.
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Polymorphism in the Bordetella pertussis
Virulence Factors P.69/Pertactin and Pertussis Toxin in The
Netherlands: Temporal Trends and Evidence for Vaccine-Driven
Evolution
*
Corresponding author. Mailing address: Research
Laboratory for Infectious Diseases, National Institute for Public
Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The
Netherlands. Phone: 31-30-274.3091. Fax: 31-30-274.4449. E-mail:
fr.mooi{at}rivm.nl.
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