Immune Cross-Opsonization Within emm Clusters Following Group A Streptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity.

Immune Cross-Opsonization Within emm Clusters Following Group A Streptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity.
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DOI:
10.1093/cid/cix599
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发表时间:
2017-10-16
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
--
通讯作者:
Smeesters PR
Smeesters PR
中科院分区:
其他
文献类型:
--
作者:
Frost HR;Laho D;Sanderson-Smith ML;Licciardi P;Donath S;Curtis N;Kado J;Dale JB;Steer AC;Smeesters PR

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在链球菌流行的群体中,单一的皮肤感染在38%的儿童中诱导了显著的免疫反应。皮肤感染后会出现交叉反应的免疫反应。这些交叉反应经常与EMM簇一致。链球菌群(GAS)皮肤感染在发展中国家尤为普遍。GAS M蛋白是免疫原性的,可引起保护性抗体,通过它可将菌株区分为>220不同的EM型。疫苗开发的一个主要障碍是传统的理解,即感染后的免疫仅限于单粒类型。然而,最近的证据导致了不同内膜类型之间的免疫交叉反应假说。我们调查了斐济学龄儿童对气性脓疱病的血清学反应,主要集中在3个主要的类群(E4,E6和D4)。感染前后血清用N-末端M肽的酶联免疫吸附试验和感染型毒株、EMM簇相关毒株和非亲缘毒株的杀菌试验检测。在53份配对血清中,有20份显示针对感染型的≥抗体效价增加了4倍。当我们对所有与集群相关的M肽进行测试时,我们发现17对血清中有9对(53%)对集群相关菌株的抗体效价也增加了4倍。当按集群分组时,E4和E6中与集群相关的EM类型的平均变化是>4倍(分别是5.9倍和19.5倍),而D4是3.8倍。这17对血清对选定的集群相关和非相关菌株进行了杀菌试验。虽然反应差异很大,但观察到了许多交叉反应杀戮的例子。这些数据表明,皮肤感染后会发生M型特异性和交叉反应的免疫反应。交叉反应免疫反应经常与EMM簇结合,为设计具有广泛覆盖面的多价疫苗提供了新的机会。
A single skin infection in group AStreptococcus–endemic settings induced a significant immune response in 38% of children. Cross-reactive immune responses occurred after skin infections. These cross-reactive responses frequently aligned withemm clusters. Group AStreptococcus (GAS) skin infections are particularly prevalent in developing nations. The GAS M protein, by which strains are differentiated into >220 differentemm types, is immunogenic and elicits protective antibodies. A major obstacle for vaccine development has been the traditional understanding that immunity following infection is restricted to a singleemm type. However, recent evidence has led to the hypothesis of immune cross-reactivity betweenemm types. We investigated the human serological response to GAS impetigo in Fijian schoolchildren, focusing on 3 majoremm clusters (E4, E6, and D4). Pre- and postinfection sera were assayed by enzyme-linked immunosorbent assay with N-terminal M peptides and bactericidal assays using the infecting-type strain,emm cluster–related strains, and nonrelated strains. Twenty of the 53 paired sera demonstrated a ≥4-fold increase in antibody titer against the infecting type. When tested against all cluster-related M peptides, we found that 9 of 17 (53%) paired sera had a ≥4-fold increase in antibody titer to cluster-related strains as well. When grouped by cluster, the mean change to cluster-relatedemm types in E4 and E6 was >4-fold (5.9-fold and 19.5-fold, respectively) but for D4 was 3.8-fold. The 17 paired sera were tested in bactericidal assays against selected cluster-related and nonrelated strains. While the responses were highly variable, numerous instances of cross-reactive killing were observed. These data demonstrate that M type–specific and cross-reactive immune responses occur following skin infection. The cross-reactive immune responses frequently align withemm clusters, raising new opportunities to design multivalent vaccines with broad coverage.
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