Development of Robust and Low-cost Vaccines Against Salmonella Paratyphi A

开发针对甲型副伤寒沙门氏菌的强效且低成本疫苗

• 批准号: 10704819
• 负责人: Rocio Canals Alvarez
• 金额: $ 81万
• 依托单位: GLAXOSMITHKLINE BIOLOGICALS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10704819
• 关键词: 5 year old; Advanced Development; Affinity; Africa; Animal Model; Antibodies; Antigens; Asia; Biological; Cause of Death; Cessation of life; Classification; Clinical Research; Clinical Trials; Data; Development; Dose; Effectiveness; Enteral; Fever; Formulation; Funding; Future; Glycoconjugates; Goals; Good Manufacturing Process; Gram-Negative Bacteria; Grant; Health; High Prevalence; Human; Immune response; Individual; Infection; Investigational Drugs; Lead; Licensing; Life; Measures; Membrane; Modeling; Mus; Oryctolagus cuniculus; Paratyphoid Fever; Pharmaceutical Preparations; Phase; Process; Production; Safety; Salmonella; Salmonella Vaccines; Salmonella enterica; Salmonella paratyphi; Salmonella typhi; Salmonella typhimurium; Sampling; Series; Structure; Technology; Testing; Toxic effect; Toxicology; Vaccines; Vesicle; Work; bactericide; cost; cross reacting material 197; diarrheal disease; enteric infection; experimental study; foodborne illness; gastrointestinal; global health; good laboratory practice; immunogenicity; improved; low and middle-income countries; manufacture; manufacturing process; phase 1 study; pre-clinical; preclinical evaluation; preclinical study; prevent; research clinical testing; scale up; vaccine candidate; vaccine safety

Project Summary / Abstract – Development of Robust and Low-cost Vaccines for Preventing S. Paratyphi A: Salmonella enterica is a Gram-negative bacterium that is a leading cause of foodborne illnesses globally. In fact, Salmonella deaths are the first cause of death within enteric and diarrheal diseases and the second cause of death in under 5-years-old. GSK Vaccines Institute for Global Health (GVGH) is developing two multivalent Pan-Salmonella vaccines based on a versatile platform, Generalized Modules for Membrane Antigens (GMMA). These vaccines target the same S. Paratyphi A antigen, but are based on different technologies, conjugate or GMMA, and are intended to provide protection from paratyphoid fever which causes potentially severe and sometimes life-threatening febrile illness. GVGH will complete three Aims within this grant structure. First, preclinical studies will be conducted to evaluate safety, reactogenicity and immunogenicity. Second, process development work for drug substance and drug product will be completed and manufacturing of both non-GMP and GMP batches will follow. Finally, a series of experiments will evaluate the immunological response in either mouse or rabbit models; the data package will include classification of antibody subclasses, affinity and bactericidal activity to provide a correlation between the quality of antibodies and functionality. The final milestone of this grant is to advance the development of a multivalent vaccine against S. Paratyphi A. This will enable GVGH to make clinical trials possible for the improvement of health for individuals worldwide.

项目总结/摘要 – 开发用于预防甲型副伤寒沙门氏菌的强效且低成本疫苗： 肠沙门氏菌是一种革兰氏阴性细菌，是食源性疾病的主要原因 事实上，沙门氏菌死亡是肠道和腹泻疾病中的首要死因， 葛兰素史克全球健康疫苗研究​​所 (GVGH) 正在研究 5 岁以下儿童死亡的第二个原因。 两种多价泛沙门氏菌疫苗基于通用平台，膜通用模块 抗原 (GMMA) 这些疫苗针对相同的甲型副伤寒沙门氏菌抗原，但基于不同的抗原。 技术、结合物或 GMMA，旨在提供预防副伤寒的保护，副伤寒会导致 二月份的疾病可能很严重，有时甚至危及生命。 GVGH 将完成该资助结构中的三个目标，首先，将进行临床前研究。 其次，评估原料药的安全性、反应原性和免疫原性。 最后，将完成药品生产，并进行非 GMP 和 GMP 批次的生产。 一系列实验将评估小鼠或兔子模型的免疫反应； 包将包括抗体亚类、亲和力和杀菌活性的分类，以提供 抗体质量和功效之间的相关性。 这笔赠款的最后一个里程碑是推进针对金黄色葡萄球菌的多价疫苗的开发。 甲型副伤寒。这将使 GVGH 能够进行改善个人健康的临床试验 全世界。