Corrected and Republished from: "A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge".
Corrected and Republished from: "A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge".
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DOI：
10.1128/iai.00846-18a
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发表时间：
2022-01-25
影响因子：
3.1
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中科院分区：
文献类型：
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目前针对肺炎链球菌的疫苗使用的是基于选定血清型的荚膜多糖的疫苗，并已导致非疫苗血清型替代疾病。我们研究了另一种不依赖血清型的方法，使用肺炎链球菌TIGR4裂解液制备的多抗原疫苗(MAV)，在诱导热休克蛋白(HSP；被认为是免疫佐剂)的条件下，通过培养后的层析步骤富含表面蛋白。蛋白质组学和免疫印迹分析表明，与标准细菌裂解物相比，MAV富含HSPs，并含有几种公认的保护性蛋白抗原，包括肺炎球菌表面蛋白A(PSPA)和肺炎溶血素(PLY)。用MAV免疫啮齿动物可诱导对多种血清型的强大抗体反应，包括非肺炎球菌结合疫苗血清型。将同源和异种肺炎链球菌分别与免疫鼠血清孵育后进行调理。在小鼠模型中，MAV主动免疫对肺炎有显著的保护作用，而被动转移MAV免疫的兔血清对同源和异种肺炎链球菌引起的败血症有显著的保护作用。用热休克步骤与不用热休克步骤制备的MAV样品进行直接比较，在蛋白抗原含量和抗原性方面没有明显差异，提示层析步骤而不是HSP诱导步骤提高了MAV的抗原性。总体而言，这些数据表明，MAV方法可能提供对肺炎链球菌的非血清型保护。
Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae.