Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in the Netherlands:: Temporal trends and evidence for vaccine-driven evolution
Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in the Netherlands:: Temporal trends and evidence for vaccine-driven evolution
复制标题
DOI：
10.1128/iai.66.2.670-675.1998
复制
发表时间：
1998-02-01
影响因子：
3.1
通讯作者：
Willems, RJL
中科院分区：
文献类型：
--
作者：
Mooi, FR;van Oirschot, H;Willems, RJL
百日咳杆菌蛋白P.69百日咳毒素（也称为百日咳毒素）和百日咳毒素是重要的毒力因子，并且已经显示在动物和人类中赋予保护性免疫。这两种蛋白质都用于新一代无细胞百日咳疫苗（ACV）中，因此研究这些蛋白质中的抗原变异程度是重要的，使用1949年至1996年期间从荷兰患者收集的菌株对P.69和百日咳毒素S1亚单位的基因进行序列分析，揭示了三种P.69和三种S1变体，它们显示出氨基酸序列的差异，P.69的多态性局限于由重复序列组成的区域，并且位于与宿主组织粘附相关的RGD基序的近端。在先前鉴定为T细胞表位的两个区域中观察到S1的变异，P.69和S1变体，与荷兰全细胞百日咳疫苗（WCV）中包括的那些相同，从20世纪50年代开始，即WCV在荷兰引入的时期，在100%的菌株中发现了P.69和S1，然而，在后来的几年中，P.69和S1的非疫苗类型逐渐取代了疫苗类型，并且在1990年至1996年期间发现了类似于90%的菌株，这些结果表明，疫苗接种选择了抗原性不同于疫苗株的菌株。接种和未接种个体的菌株分析表明，WCV对疫苗型P.69菌株的保护优于非疫苗型菌株（P = 0.024），ACV含有P.69和S1型，仅在10%的荷兰B中发现。我们的研究结果为百日咳在高度接种疫苗的人群中重新出现提供了新的线索，并可能对WCV和ACV的长期疗效产生重大影响。
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 SI 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 similar to 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.