Protection induced by pneumococcal surface protein A (PspA) is enhanced by conjugation to a Streptococcus pneumoniae capsular polysaccharide

Protection induced by pneumococcal surface protein A (PspA) is enhanced by conjugation to a Streptococcus pneumoniae capsular polysaccharide
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DOI:
10.1016/j.vaccine.2008.03.038
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发表时间:
2008-06-02
期刊:
影响因子:
5.5
通讯作者:
Tanizaki, Martha M.
Tanizaki, Martha M.
中科院分区:
医学3区
文献类型:
--
作者:
Csordas, Fatima C. L.;Perciani, Catia T.;Tanizaki, Martha M.

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目前可用的抗肺炎球菌疫苗是基于荚膜多糖(PS)的,其是纯的或与载体蛋白缀合的。结合疫苗是昂贵的产品,特别是在肺炎球菌的情况下,其中合理的覆盖范围需要7至13种血清型。为了用更少的组分获得更高的覆盖率,我们评估了与荚膜多糖血清型23 F缀合的肺炎球菌表面蛋白A(PspA)的免疫原性,旨在诱导针对两种组分的免疫应答。用PS23 F-rPspA 1缀合物免疫的小鼠产生抗PS和rPspA 1的抗体,与游离PS获得的抗体相当或略高。用致死剂量的携带同源PspA的强毒株攻击的免疫动物显示,PS23 F-rPspA 1缀合物诱导的存活率高于单独的rPspA 1或与PS的组合。这种增加的保护显示与抗体结合肺炎球菌表面和诱导补体沉积的能力增强相关。我们的研究结果表明,使用PS-PspA缀合物可能是一种以较少的组分增加对肺炎球菌的覆盖率的方法。(c)2008爱思唯尔有限公司版权所有。
The currently available anti-pneumococcal vaccines are based on capsular polysaccharide (PS), plain or conjugated to a carrier protein. Conjugated vaccines are expensive products, especially in the case of pneumococcus, in which reasonable coverage requires from 7 to 13 serotypes. To obtain increased coverage with fewer components, we evaluated the immunogenicity of the pneumococcal surface protein A (PspA), conjugated to capsular polysaccharide serotype 23F, aiming at induction of an immune response against both components. Mice immunized with PS23F-rPspA1 conjugate produced antibodies against both PS and rPspA1, comparable or slightly higher than that obtained by free PS. The immunized animals challenged with a lethal dose of a virulent strain bearing a homologous PspA, showed that the PS23F-rPspA1 conjugate induced higher survival than rPspA1 alone or in combination with PS. This increased protection was shown to correlate with the enhanced capacity of the antibodies to bind to the pneumococcal surface and to induce complement deposition. Our results indicate that the use of PS-PspA conjugates may be a way to increase coverage against pneumococci with fewer components. (c) 2008 Elsevier Ltd. All rights reserved.