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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要肺炎球菌疾病对年轻人和老年人的影响不成比例。值得注意的是，高龄和甲型流感病毒感染协同作用，增强肺炎球菌肺部感染的易感性。事实上，老年人（> 65 岁）占流感和流感死亡人数的 70-85%。肺炎。预计到 2050 年，全球这一弱势群体将达到 20 亿，新的增强对继发性肺炎球菌肺炎和肺炎球菌的抵抗力的预防方法更普遍的疾病是需要的。背景：普法伊弗小组设计了一种新型疫苗配方，称为多糖脂质体封装（LEPS），旨在考虑到肺炎链球菌细菌血清型的广度和使情况复杂化的独特的进展特征肺炎球菌疾病的治疗选择。意义/创新：LEPS 公式结合了两者多糖和蛋白质抗原，这是一种创新方法，可提供胶囊特异性针对其他血清型和疾病进展阶段的免疫和交叉保护。因为这个候选疫苗在正常年龄小鼠中的能力已达到并超过 Prevnar-13，随附的应用程序具有与 Elsa Bou Ghanem 博士的互补合作，以测试假设给老年小鼠接种 LEPS 颗粒疫苗会诱导强烈的免疫反应相对于当前的肺炎球菌疫苗制剂。这一假设将通过以下方式得到彻底解决：三个具体目标： 1) 使用老年人肺炎模型扩大 LEPS 平台的血清型覆盖范围对小鼠进行详细的免疫学评估以揭示机制； 2) 评估次生细菌使用 LEPS 平台观察老年小鼠的肺炎； 3) 测试 LEPS 制剂的鼻内递送不同年龄小鼠的肺炎球菌疾病。宿主存活、临床疾病评分、器官特异性细菌随着时间的推移，将测量整个疫苗的负担和感染严重程度（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（即 PPSV 和 PCV），在这种情况下，我们将拥有支持转化进展所需的重要临床前数据。