Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniae
Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniae
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DOI：
10.1128/iai.01103-06
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Paton, James C.
中科院分区：
文献类型：
--
作者：
Ogunniyi, Abiodun D.;Grabowicz, Marcin;Paton, James C.
目前全球努力的重点是探索替代肺炎球菌疫苗战略，目的是在不影响疗效的情况下解决现有配方的缺点。一种这样的策略涉及使用所有血清型通用的一个或多个肺炎球菌蛋白抗原，以提供廉价的、非血清型依赖的保护。在这项研究中，我们在侵袭性疾病模型中评估了PDB(一种肺炎毒素类)、PSPA、PSPC(CbpA)、PhtB和PhtE免疫小鼠的保护效果。这些抗原在明胶佐剂中单独或以各种组合给予。在两个品系的小鼠中，评估了对强毒2型和6A型毒株对腹膜攻击的保护作用。我们的发现表明，在某些情况下，不同的单独蛋白质提供了最好(和最差)的保护。然而，在许多情况下，通过使用多个蛋白质可以看到协同/相加效应，即使单个蛋白质本身显示的价值很小。例如，PDB和PSPA、PDB和PSPC或PSPA和PSPC组合免疫的小鼠的中位存活时间显著长于任何单一抗原免疫的小鼠。到目前为止，PDB、PSPA和PSPC的组合提供了最佳保护。
Current global efforts are focused on exploring alternative pneumococcal vaccine strategies, aimed at addressing the shortcomings of existing formulations, without compromising efficacy. One such strategy involves the use of one or more pneumococcal protein antigens common to all serotypes, to provide cheap, non-serotype-dependent protection. In this study, we evaluated the protective efficacy of immunization of mice with PdB (a pneumolysin toxoid), PspA, PspC (CbpA), PhtB, and PhtE in an invasive-disease model. The antigens were administered in alum adjuvant, either alone or in various combinations. Protection against intraperitoneal challenge with virulent type 2 and 6A strains was assessed in two murine strains. Our findings show that in some situations, different individual proteins gave the best (and worst) protection. However, in many cases, a synergistic/additive effect was seen by using multiple proteins even where the individual proteins showed little value by themselves. For instance, the median survival times for mice immunized with combinations of PdB and PspA, PdB and PspC, or PspA and PspC were significantly longer than those for mice immunized with any of the single antigens. To date, the combination of PdB, PspA, and PspC offers the best protection.