Liposomal Encapsulation Vaccine Design for Pneumococcal Disease in Aged Subjects

项目总结 肺炎球菌病对年轻人和老年人的影响是不成比例的。值得注意的是，高龄 与甲型流感病毒感染协同作用，增加肺炎球菌肺部感染的易感性。 事实上，老年人(65岁)占因流感和其他疾病死亡的70%-85%。 肺炎。据预测，到2050年，全球弱势群体将达到20亿。 预防措施，提高对继发性肺炎球菌肺炎和肺炎球菌的抵抗力 更广泛地说，疾病是需要的。背景：Pfeifer团队已经设计出一种新的疫苗 制剂，称为脂质体包囊多糖(LEPS)，旨在解释 肺炎链球菌细菌血清型的广泛性和使其复杂化的独特进展情况 肺炎链球菌病的治疗选择。意义/创新：LEPS方案将两者结合在一起 多糖和蛋白质抗原，这是一种创新的方法，提供了胶囊特异性 对其他血清型和疾病进展阶段的免疫和交叉保护。因为这件事 候选疫苗已经在正常年龄的小鼠身上赶上并超过了Prevnar-13的能力， 封闭式应用程序与Elsa Bou Garem博士进行补充合作，以测试 假设用LEPS颗粒接种老年小鼠将产生强大的免疫反应 相对于目前的肺炎球菌疫苗配方。这一假设将通过以下途径得到彻底解决 三个具体目标：1)利用LEPS平台扩大老年肺炎模型的血清型覆盖范围 用详细的免疫学评估揭示机制的小鼠；2)评估次级细菌 使用LEPS平台的老年小鼠肺炎；以及3)LEPS制剂的鼻腔给药试验 对不同年龄的小鼠肺炎球菌病的治疗。宿主存活率、临床疾病评分、器官特异性细菌 负担和其他感染严重程度的指标(器官病理)将随着时间的推移跨疫苗进行测量 和非疫苗肺炎球菌株，以评估血清型特异性保护以及交叉保护。 成功的结果将包括超越当前疫苗选择的治疗效果(即PPSV和 PCV)，在这种情况下，我们将拥有支持翻译进展所需的重要临床前数据。

PROJECT SUMMARY Pneumococcal disease has a disproportional impact upon the young and elderly. Notably, advanced age and influenza A virus infection act synergistically to enhance susceptibility to pneumococcal lung infections. Indeed, older adults (>65 years old) account for 70-85% of deaths due to the combination of influenza and pneumonia. As this vulnerable population is projected to reach two billion worldwide by 2050, novel preventative approaches that boost resistance to secondary pneumococcal pneumonia, and pneumococcal disease more generally, are needed. Background: The Pfeifer group has engineered a novel vaccine formulation, termed Liposomal Encapsulation of Polysaccharides (LEPS), designed to account for both the breadth of Streptococcus pneumoniae bacterial serotypes and the unique progression profiles that complicate treatment options for pneumococcal disease. Significance/Innovation: The LEPS formulation combines both polysaccharide and protein antigens, which is an innovative approach that provides both capsule specific immunity and cross protection against other serotypes and stages of disease progression. Because this vaccine candidate has matched and exceeded the capabilities of Prevnar-13 in normal-aged mice, the enclosed application features a complementary collaboration with Dr. Elsa Bou Ghanem to test the Hypothesis that vaccination of elderly mice with the LEPS particle will induce a robust immune response relative to current pneumococcal vaccine formulations. This hypothesis will be thoroughly addressed through three specific Aims: 1) Expand Serotype Coverage with the LEPS Platform in Pneumonia Models using Aged Mice with Detailed Immunological Assessment to Reveal Mechanism; 2) Assess Secondary Bacterial Pneumonia within Aged Mice using the LEPS Platform; and 3) Test Intranasal Delivery of LEPS Formulations for Pneumococcal Disease in Mice across Age. Host survival, clinical disease score, organ-specific bacterial burden, and other indicators of infection severity (organ pathology) will be measured over time across vaccine and non-vaccine pneumococcal strains to assess serotype-specific protection as well as cross protection. Successful outcomes will include treatment effectiveness beyond current vaccine options (i.e., PPSV and PCV), in which case, we will have important preclinical data needed to support translational progression.