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

项目概要/摘要- 开发用于预防S的稳健和低成本疫苗。甲型副伤寒： 肠道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 在全球事实上，沙门氏菌死亡是肠道和消化道疾病的第一死因， 五岁以下儿童的第二大死因GSK全球健康疫苗研究所（GVGH） 基于通用平台的两种多价泛沙门氏菌疫苗，通用膜模块 抗原（GMMA）。这些疫苗针对相同的S。甲型副伤寒抗原，但基于不同的 技术，共轭或GMMA，并旨在提供保护，从副伤寒， 可能严重，有时危及生命的发热性疾病。 GVGH将在此赠款结构中完成三个目标。首先，将进行临床前研究， 评价安全性、反应原性和免疫原性。二是原料药工艺开发工作 将完成药品生产，随后将生产非GMP和GMP批次。最后， 一系列实验将评估小鼠或兔模型中的免疫应答;数据 包将包括抗体亚类的分类，亲和力和杀菌活性，以提供一个 抗体质量和功能之间的相关性。 这项资助的最后一个里程碑是推进抗沙门氏菌多价疫苗的开发。 甲型副伤寒这将使GVGH能够进行临床试验，以改善个人健康 国际吧

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.