Csordas Fátima C L, Perciani Cátia T, Darrieux Michelle, Gonçalves Viviane M, Cabrera-Crespo Joaquim, Takagi Mickie, Sbrogio-Almeida Maria E, Leite Luciana C C, Tanizaki Martha M
Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brasil 1500, CEP 05503, São Paulo, Brazil.
Vaccine. 2008 Jun 2;26(23):2925-9. doi: 10.1016/j.vaccine.2008.03.038. Epub 2008 Apr 9.
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.
目前可用的抗肺炎球菌疫苗基于荚膜多糖（PS），其可为单纯形式或与载体蛋白偶联。偶联疫苗价格昂贵，尤其是对于肺炎球菌而言，因为要实现合理的覆盖率需要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23F血清型荚膜多糖偶联的肺炎球菌表面蛋白A（PspA）的免疫原性，旨在诱导针对这两种组分的免疫反应。用PS23F-rPspA1偶联物免疫的小鼠产生了针对PS和rPspA1的抗体，其水平与游离PS相当或略高。用携带同源PspA的致死剂量的强毒株攻击免疫动物，结果表明PS23F-rPspA1偶联物诱导的存活率高于单独的rPspA1或rPspA1与PS联合使用时的存活率。这种增强的保护作用与抗体结合肺炎球菌表面及诱导补体沉积的能力增强相关。我们的结果表明，使用PS-PspA偶联物可能是一种用更少组分提高肺炎球菌覆盖率的方法。
