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

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.