Fusion proteins containing family 1 and family 2 PspA fragments elicit protection against Streptococcus pneumoniae that correlates with antibody-mediated enhancement of complement deposition
Fusion proteins containing family 1 and family 2 PspA fragments elicit protection against Streptococcus pneumoniae that correlates with antibody-mediated enhancement of complement deposition
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DOI：
10.1128/iai.00940-07
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发表时间：
2007-12-01
影响因子：
3.1
通讯作者：
Leitel, L. C. C.
中科院分区：
文献类型：
--
作者：
Darrieux, M.;Miyaji, E. N.;Leitel, L. C. C.
PspA 是一种重要的肺炎球菌候选疫苗，能够在不同的动物模型中产生保护作用。由于其结构多样性，基于 PspA 的疫苗应至少包含来自两个主要家族（1 和 2）的每个片段，以便获得更广泛的保护。在目前的工作中，我们测试了含有家族 1 和 2 融合部分（PspA1ABC-4B 和 PspA1ABC-3AB）PspA 片段的 PspA 杂交体诱导针对带有不同 PspA 片段的肺炎球菌的保护的潜力。与针对 PspA 家族 1 (PspA1ABC) 和 PspA 家族 2 (PspA3ABC) 片段的血清相比，用这些杂合 PspA 片段免疫的小鼠血清能够增加 C3 在带有来自两个家族的 PspA 片段的肺炎球菌上的 C3 沉积，而后者仅在同一家族内有效。尽管 PspA 杂种能够通过携带不同 PspA 片段的菌株来扩展对肺炎球菌感染的保护，但家族 2 引发的免疫是进化枝依赖性的，这表明来自家族 2 进化枝 3 和 4 的 PspA 片段都应包含在综合性 PspA 疫苗中。这些结果表明，PspA 融合蛋白构成了未来基于 PspA 的抗肺炎球菌疫苗的有效免疫策略，因为它们能够扩展源自单个转录物的蛋白质提供的保护。
PspA is an important pneumococcal vaccine candidate that is capable of inducing protection in different animal models. Because of its structural diversity, a PspA-based vaccine should contain at least one fragment from each of the two major families (1 and 2) in order to elicit broader protection. In the present work, we have tested the potential of PspA hybrids containing fused portions of family 1 and 2 (PspA1ABC-4B and PspA1ABC-3AB) PspA fragments to induce protection against pneumococci bearing distinct PspA fragments. Sera from mice immunized with these hybrid PspA fragments were able to increase C3 deposition on pneumococci bearing PspA fragments from both families, in contrast with sera made against the PspA family 1 (PspA1ABC) and PspA family 2 (PspA3ABC) fragments, which were effective only within the same family. Although PspA hybrids were able to extend protection against pneumococcal infection with strains bearing diverse PspA fragments, the immunity elicited by family 2 was clade dependent, suggesting that PspA fragments from family 2 clades 3 and 4 should both be included in a comprehensive PspA vaccine. These results indicate that PspA fusion proteins constitute an efficient immunization strategy for future PspA-based anti-pneumococcal vaccines since they are able to extend protection provided by a protein derived from a single transcript.