Immunization of Mice with Single PspA Fragments Induces Antibodies Capable of Mediating Complement Deposition on Different Pneumococcal Strains and Cross-Protection
Immunization of Mice with Single PspA Fragments Induces Antibodies Capable of Mediating Complement Deposition on Different Pneumococcal Strains and Cross-Protection
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DOI：
10.1128/cvi.00430-09
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发表时间：
2010-03-01
影响因子：
--
通讯作者：
Miyaji, Eliane N.
中科院分区：
文献类型：
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作者：
Moreno, Adriana T.;Oliveira, Maria Leonor S.;Miyaji, Eliane N.
PspA是一种重要的候选疫苗，具有血清型不依赖的免疫，以对抗肺炎球菌感染。根据序列亲缘关系，将PspA划分为3科6支。我们之前通过Western blot分析解决了针对含有PspA n端和PspA富含脯氨酸区域的PspA片段的抗体的交叉反应性，并报道了抗PspA4和抗PspA5能够识别所有分析的进化枝中表达PspA蛋白的肺炎球菌。我们现在已经分析了这些抗体在体外完整细菌上结合和介导补体沉积的功能能力。我们的研究结果表明，PspA4和PspA5都能引发抗体，这些抗体能够有效地结合并介导从支系1到5携带PspA蛋白的肺炎球菌菌株的补体沉积。此外，用PspA4和PspA5免疫的小鼠可以抵抗来自两个主要家族的PspA蛋白的鼻内致死攻击。因此，PspA4和PspA5能够在体外诱导出具有高度交叉反应性的抗体，这体现在小鼠的交叉保护上。我们还分析了富含脯氨酸的保守区域内的非脯氨酸（NonPro）片段对抗PspA抗体反应性的贡献，结果表明n端α -螺旋区、脯氨酸重复片段和NonPro区域可以影响PspA抗体的交叉反应性程度。
PspA is an important candidate for a vaccine with serotype-independent immunity against pneumococcal infections. Based on sequence relatedness, PspA has been classified into three families comprising six clades. We have previously addressed the cross-reactivity of antibodies against PspA fragments containing the N-terminal and proline-rich regions of PspA from clades 1 to 5 (PspA1, PspA2, PspA3, PspA4, and PspA5) by Western blot analysis and reported that anti-PspA4 and anti-PspA5 were able to recognize pneumococci expressing PspA proteins from all of the clades analyzed. We have now analyzed the functional capacity of these antibodies to bind and to mediate complement deposition on intact bacteria in vitro. Our results show that both PspA4 and PspA5 elicit antibodies that are able to bind and to mediate complement deposition efficiently on pneumococcal strains bearing PspA proteins from clades 1 to 5. Moreover, mice immunized with PspA4 and PspA5 were protected against an intranasal lethal challenge with strains expressing PspA proteins from the two major families. PspA4 and PspA5 are thus able to induce antibodies with a high degree of cross-reactivity in vitro, which is reflected in cross-protection of mice. We have also analyzed the contribution of the nonproline (NonPro) block within the conserved proline-rich region to the reactivity of anti-PspA antibodies, and the results indicate that N-terminal alpha-helical region, the blocks of proline repeats, and the NonPro region can influence the degree of cross-reactivity of antibodies to PspA.