Vaccine escape recombinants emerge after pneumococcal vaccination in the united states
Vaccine escape recombinants emerge after pneumococcal vaccination in the united states
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DOI：
10.1371/journal.ppat.0030168
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发表时间：
2007-11-01
期刊：
影响因子：
6.7
通讯作者：
Beall, Bernard
中科院分区：
文献类型：
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作者：
Brueggemann, Angela B.;Pai, Rekha;Beall, Bernard
七价肺炎球菌结合疫苗(PCV7)于2000年引入美国，显著减少了侵袭性肺炎球菌疾病；然而，非疫苗血清型侵袭性疾病的发病率，特别是由于19A血清型，增加了。19A血清型增加的部分原因可以解释为在疫苗实施之前在美国(至少自1990年以来)一直在美国传播的一种基因的扩大，但也可以通过一种新的“疫苗逃逸重组”肺炎球菌株的出现来解释。该毒株的基因型别以前只与疫苗血清4型有关，但现在表达的是非疫苗血清型19A胶囊。根据先前通过衣壳基因座重组进行衣壳转换的证据，可以从单个肺炎球菌菌株的DNA序列中识别导致这种新的血清型/基因型组合的遗传事件。因此，这项研究的目的是描述导致疫苗衣壳类型转变为非疫苗衣壳类型的衣壳基因座上假定的重组事件(S)。对51株疫苗逃逸(后代)、受体和假定供体肺炎球菌的衣壳基因侧翼区进行了测序，发现了一个39kb的重组片段，它包括衣壳基因座、侧翼区和两个相邻的青霉素结合蛋白，从而导致了衣壳开关和青霉素不敏感的单一遗传事件。自2003年以来，已检测到37个此类疫苗逃逸毒株，其中一些已经进一步进化。此外，2005年出现了两种新的19A血清型疫苗逃逸株。据我们所知，这是第一次在体内记录到单个重组事件同时导致血清型改变和青霉素不敏感。从长远来看，疫苗通过衣壳基因重组逃逸有可能降低PCV7的有效性。
The heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the United States ( US) in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation ( and other countries since at least 1990), but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s) at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape ( progeny), recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.