Liposomal Encapsulation Vaccine Design for Pneumococcal Disease in Aged Subjects

用于老年受试者肺炎球菌疾病的脂质体封装疫苗设计

• 批准号: 10676202
• 负责人: Blaine Pfeifer
• 金额: $ 40.3万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-04 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676202
• 关键词: Address; Age; Antibody Response; Antigens; Bacteremia; Bacterial Infections; Bacterial Pneumonia; Bacterial Proteins; Basic Science; Benign; Biomedical Engineering; Carrier Proteins; Cell physiology; Cessation of life; Chemical Engineering; Clinical; Collaborations; Communicable Diseases; Communities; Conjugate Vaccines; Coupling; Data; Development; Disease; Disease Progression; Economics; Elderly; Encapsulated; Engineering; Formulation; Gene Expression Profile; Goals; Grant; Health; Hospitalization; Human; Immune; Immune response; Immunity; Immunization; Immunologics; Immunology; Individual; Infection; Influenza; Influenza A virus; Joints; Licensing; Liposomes; Lung; Lung infections; Marketing; Measures; Meningitis; Methodology; Microbiology; Mus; Nasopharynx; Organ; Outcome; Pathology; Phenotype; Pneumococcal Infections; Pneumococcal Pneumonia; Pneumococcal conjugate vaccine; Pneumococcal vaccine; Pneumonia; Polysaccharides; Polyvalent pneumococcal vaccine; Population; Predisposition; Prevention strategy; Prevnar; Printing; Productivity; Prophylactic treatment; Proteins; Publishing; Reporting; Research; Resistance; Risk; Seasons; Secondary to; Serotyping; Severities; Streptococcus pneumoniae; Surface; Technology; Testing; Time; Translating; Treatment Effectiveness; Universities; Vaccination; Vaccine Design; Vaccines; Virulence; Virus Diseases; Vulnerable Populations; Work; aged; capsule; co-infection; cross immunity; cross reacting material 197; design; expectation; global health; human old age (65+); immunogenic; immunosenescence; improved; innovation; liposomal delivery; novel; novel vaccines; particle; pathogen; pneumonia model; pre-clinical; prophylactic; standard of care; stem; success; translational progress; vaccination outcome; vaccine candidate; vaccine formulation; vaccine platform

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.

项目摘要 肺炎球菌疾病对年轻人和老年人的影响不成比例。尤其是高龄 和甲型流感病毒感染协同作用以增强对肺炎球菌肺部感染的易感性。 事实上，老年人（>65岁）占因流感和流感病毒结合而死亡的70-85%。 肺炎预计到2050年，全球这一脆弱人口将达到20亿， 预防方法，提高对继发性肺炎球菌肺炎和肺炎球菌肺炎的抵抗力， 更普遍的疾病是需要的。背景：Pfeifer小组设计了一种新型疫苗 制剂，称为多糖脂质体包封（LEPS），旨在考虑两个 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特征， 肺炎球菌病的治疗选择。意义/创新：LEPS配方结合了 多糖和蛋白质抗原，这是一种创新的方法，既提供胶囊特异性 免疫力和针对其他血清型和疾病进展阶段的交叉保护。因为这 候选疫苗在正常年龄小鼠中的能力与Prevnar-13相当， 随附的应用程序与艾尔莎布加尼姆博士互补合作，以测试 假设用LEPS颗粒接种老年小鼠将诱导强烈的免疫应答 相对于目前的肺炎球菌疫苗制剂。这一假设将通过 三个具体目标：1）在使用老年人的肺炎模型中，使用LEPS平台扩大血清型覆盖率 对小鼠进行详细的免疫学评估以揭示机制; 2）评估继发性细菌 使用LEPS平台在老年小鼠内的肺炎;和3）测试LEPS制剂的鼻内递送 小鼠肺炎球菌疾病的研究宿主存活率、临床疾病评分、器官特异性细菌 随着时间的推移，将在疫苗之间测量感染严重程度（器官病理学）的其他指标 和非疫苗肺炎球菌菌株，以评估细菌型特异性保护以及交叉保护。 成功的结果将包括超越目前疫苗选择的治疗有效性（即，PPSV和 PCV），在这种情况下，我们将获得支持翻译进展所需的重要临床前数据。