Identification of group B streptococcal Sip protein, which elicits cross-protective immunity

Identification of group B streptococcal Sip protein, which elicits cross-protective immunity
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DOI:
10.1128/iai.68.10.5610-5618.2000
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发表时间:
2000-10-01
影响因子:
3.1
通讯作者:
Martin, D
Martin, D
中科院分区:
医学2区
文献类型:
--
作者:
Brodeur, BR;Boyer, M;Martin, D

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在对基因组文库进行免疫学筛选后,鉴定了B族链球菌(GBS)的蛋白质,其命名为Sip,用于表面免疫原性蛋白,其不同于先前描述的表面蛋白。使用Sip特异性单克隆抗体的免疫印迹表明,在每个测试的GBS菌株中存在大小没有变化的分子量约为53 kDa的蛋白带。所有9种GBS血清型的代表都包括在菌株组中。sip基因的开放阅读框为1,305个核苷酸,编码432个氨基酸残基的多肽,pI为6.84,分子量为45.5 kDa。sip基因在GBS中高度保守,同源性为98%。N-末端氨基酸测序也表明存在25个氨基酸的信号肽,其在成熟蛋白中被切割。更重要的是,用重组Sip蛋白免疫有效地保护CD-1小鼠免受六种血清型Ia/c、Ib、II/R、III、V和VI的GBS菌株的致命攻击。本研究中提供的数据表明,这种高度保守的蛋白质诱导针对GBS感染的交叉保护性免疫,并强调其作为通用候选疫苗的潜力。
A protein of group B streptococci (GBS), named Sip for surface immunogenic protein, which is distinct from previously described surface proteins, was identified after immunological screening of a genomic library. Immunoblots using a Sip-specific monoclonal antibody indicated that a protein band with an approximate molecular mass of 53 kDa which did not vary in size was present in every GBS strain tested. Representatives of all nine GBS serotypes were included in the panel of strains. Cloning and sequencing of the sip gene revealed an open reading frame of 1,305 nucleotides coding for a polypeptide of 432 amino acid residues, with a calculated pi of 6.84 and molecular mass of 45.5 kDa, Comparison of the nucleotide sequences from six different strains confirmed with 98% identity that the sip gene is highly conserved among GBS isolates. N-terminal amino acid sequencing also indicated the presence of a 25-amino-acid signal peptide which is cleaved in the mature protein. More importantly, immunization with the recombinant Sip protein efficiently protected CD-I mice against deadly challenges with six GBS strains of serotypes Ia/c, Ib, II/R, III, V, and VI. The data presented in this study suggest that this highly conserved protein induces cross-protective immunity against GBS infections and emphasize its potential as a universal vaccine candidate.