Falugi Fabiana, Zingaretti Chiara, Pinto Vittoria, Mariani Massimo, Amodeo Laura, Manetti Andrea G O, Capo Sabrina, Musser James M, Orefici Graziella, Margarit Immaculada, Telford John L, Grandi Guido, Mora Marirosa
Novartis Vaccines, Siena, Italy.
J Infect Dis. 2008 Dec 15;198(12):1834-41. doi: 10.1086/593176.
We previously reported that group A Streptococcus (GAS) pili are the T antigens described by Rebecca Lancefield. We also showed that these pili, constituted by backbone, ancillary 1, and ancillary 2 proteins, confer protection against GAS challenge in a mouse model.
We evaluated pilus distribution and conservation by sequencing the subunits of 39 new GAS isolates and used immunoblot analysis and agglutination assays to define the specificity of T sera to pilus subunits.
GAS pili are encoded by 9 different islands within which backbone protein, ancillary protein 1, and ancillary protein 2 cluster in 15, 16, and 5 variants, respectively. Immunoblot and agglutination assays revealed that T type is determined by the backbone variant. This observation enabled us to set up a simple polymerase chain reaction assay to define the T type of GAS isolates.
We propose the use of a tee gene sequence typing, analogous to the emm gene typing, as a valuable molecular tool that could substitute for the serological T classification of GAS strains. From our sequence analysis and from recent epidemiological data, we estimate that a vaccine comprising a combination of 12 backbone variants would protect against > 90% of currently circulating strains.
我们之前报道过A组链球菌(GAS)菌毛是丽贝卡·兰斯菲尔德所描述的T抗原。我们还表明,这些由主干蛋白、辅助蛋白1和辅助蛋白2构成的菌毛,在小鼠模型中能提供针对GAS攻击的保护作用。
我们通过对39株新的GAS分离株的亚基进行测序来评估菌毛的分布和保守性,并使用免疫印迹分析和凝集试验来确定T血清对菌毛亚基的特异性。
GAS菌毛由9个不同的岛编码,其中主干蛋白、辅助蛋白1和辅助蛋白2分别以15种、16种和5种变体聚类。免疫印迹和凝集试验表明,T型由主干变体决定。这一观察结果使我们能够建立一种简单的聚合酶链反应试验来确定GAS分离株的T型。
我们建议使用类似于emm基因分型的tee基因序列分型,作为一种有价值的分子工具,可替代GAS菌株的血清学T分类。根据我们的序列分析和近期的流行病学数据,我们估计,一种包含12种主干变体组合的疫苗将能抵御>90%的当前流行菌株。