A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae.
A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae.
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DOI：
10.1016/j.vaccine.2011.05.051
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发表时间：
2011-07-26
期刊：
影响因子：
5.5
通讯作者：
Poolman, Jan T.
中科院分区：
文献类型：
--
作者：
Denoel, Philippe;Philipp, Mario T.;Doyle, Lara;Martin, Dale;Carletti, Georges;Poolman, Jan T.
肺炎链球菌引起的感染是全世界死亡的一个主要原因。设想以蛋白质为基础的肺炎球菌疫苗取代或补充目前的以多糖为基础的疫苗。在这种情况下，解毒溶肺素（dPly）和肺炎球菌组氨酸三联体蛋白D （PhtD）是两种可能被纳入肺炎球菌疫苗的候选物。在本研究中，在恒河猴肺炎模型中评估了phd - dply疫苗的保护效果。动物分别用佐剂系统AS02配制的10µg PhD和10µg dPly或单独用AS02免疫两次，然后用19F肺炎球菌菌株攻毒。蛋白质疫苗组的存活率明显更高，似乎与在攻击后第一周内大大减少细菌负荷的能力有关。疫苗接种引起了高浓度的抗phtd和抗ply抗体，并且发现了存活与抗体水平之间的联系。综上所述，as02佐剂dr - dply疫苗对肺炎链球菌引起的肺炎具有保护作用。可能这种保护至少部分是由PhtD和ply特异性抗体介导的。
Infections caused by Streptococcus pneumoniae are a major cause of mortality throughout the world. Protein-based pneumococcal vaccines are envisaged to replace or complement the current polysaccharide-based vaccines. In this context, detoxified pneumolysin (dPly) and pneumococcal histidine triad protein D (PhtD) are two potential candidates for incorporation into pneumococcal vaccines. In this study, the protective efficacy of a PhtD-dPly vaccine was evaluated in a rhesus macaque (Macaca mulatta) model of pneumonia. The animals were immunized twice with 10 µg of PhD and 10 µg of dPly formulated in the Adjuvant System AS02 or with AS02 alone, before they were challenged with a 19F pneumococcal strain. The survival was significantly higher in the protein-vaccinated group and seemed to be linked to the capacity to greatly reduce bacterial load within the first week post-challenge. Vaccination elicited high concentrations of anti-PhtD and anti-Ply antibodies and a link was found between survival and antibody levels. In conclusion, AS02-adjuvanted PhtD-dPly vaccine protects against S. pneumoniae-induced pneumonia. It is probable that the protection is at least partially mediated by PhtD- and Ply-specific antibodies.
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