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首页> 外文期刊>Vaccine >The diversity of the proline-rich domain of pneumococcal surface protein A (PspA): Potential relevance to a broad-spectrum vaccine
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The diversity of the proline-rich domain of pneumococcal surface protein A (PspA): Potential relevance to a broad-spectrum vaccine

机译：富含肺炎球菌表面蛋白A（PSPA）的富含脯氨酸域的多样性：与广谱疫苗的潜在相关性

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Pneumococcal surface protein A (PspA) is a surface exposed, highly immunogenic protein of Streptococcus pneumoniae. Its N-terminal alpha-helical domain (al-ID) elicits protective antibody in humans and animals that can protect mice from fatal infections with pneumococci and can be detected in vitro with opsonophagocytosis assays. The proline-rich domain (PRD) in the center of the PspA sequence can also elicit protection. This study revealed that although the sequence of PRD was diverse, PRD from different pneumococcal isolates contained many shared elements. The inferred amino acid sequences of 123 such PRDs, which were analyzed by assembly and alignment-free (AAF) approaches, formed three PRD groups. Of these sequences, 45 were classified as Group 1, 19 were classified as Group 2, and 59 were classified as Group 3. All Group 3 sequences contained a highly conserved 22-amino acid non-proline block (NPB). A significant polymorphism was observed, however, at a single amino acid position within NPB. Each of the three PRD groups had characteristic patterns of short amino acid repeats, with most of the repeats being found in more than one PRD group. One of these repeats, PKPEQP as well as the NPB were previously shown to elicit protective antibodies in mice. In this study, we found that sera from 12 healthy human adult volunteers contained antibodies to all three PRD groups. This suggested that a PspA-containing vaccine containing carefully selected PRDs and od-IDs could redundantly cover the known diversity of PspA. Such an approach might reduce the chances of PspA variants escaping a PspA vaccine's immunity. (C) 2018 The Author(s). Published by Elsevier Ltd.
机译：肺炎球菌表面蛋白A（PSPA）是肺炎链球菌的表面暴露，高度免疫原蛋白。其N末端α-螺旋域（AL-ID）在人体和动物中引发保护抗体，其可以保护小鼠免受致命感染的肺炎球菌，并且可以在体外检测具有OPSONococococytosis测定。 PSPA序列中心的富含脯氨酸域（PRD）也可以引起保护。本研究表明，虽然PRD的序列是多样的，但来自不同肺炎球菌分离物的PRD包含许多共用元件。通过组装和无组装（AAF）接近的推断氨基酸序列为123个这样的PRD，形成三个PRD组。在这些序列中，将45分为第1组，将19组分类为第2组，并且59分为第3组。所有第3组序列含有高度保守的22-氨基酸非脯氨酸嵌段（NPB）。然而，在NPB内的单个氨基酸位置观察到显着的多态性。三个PRD组中的每一个具有短氨基酸重复的特征模式，大部分重复在一个以上的PRD组中被发现。其中一种重复，PKPEQP以及NPB先前显示出小鼠中的保护抗体。在这项研究中，我们发现来自12名健康人类成人志愿者的血清含有所有三个PRD组的抗体。这表明含PSPA的疫苗仔细选择的PRD和OD-ID可以冗余地涵盖已知的PSPA多样性。这种方法可能会降低PSPA变体逃避PSPA疫苗免疫的机会。 （c）2018年作者。 elsevier有限公司出版

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