Exploiting genetics, genomics, and immunological responses to construct novel conjugate vaccines against Salmonella Paratyphi A; an emerging global health threat

A second major cause of enteric fever—the bacterium *Salmonella* Paratyphi A—currently has no licensed vaccine, while its better-known relative *Salmonella* Typhi does. This fellowship aims to close that gap by building the first effective conjugate vaccines against Paratyphi A from the ground up. The problem is straightforward: Paratyphi A causes a febrile illness indistinguishable from typhoid, yet it remains poorly understood. Without a vaccine, people in endemic regions of Asia face a preventable disease that current control measures cannot stop. The researcher will first map the genetic diversity of Paratyphi A circulating today, using samples from collaborators across Asia. This reveals which surface structures are stable enough to target with a vaccine. A key obstacle is that Paratyphi A’s O-antigen—the main component of all experimental vaccines against it—can switch forms, potentially allowing the bacterium to evade immune responses. The project will uncover the mechanism behind this variation and test whether it actually helps the pathogen escape immunity. Finally, the researcher will attach a panel of newly identified immunogenic proteins to the O-antigen, creating bespoke conjugate vaccines designed to provoke a strong, lasting immune response. If successful, this work could produce a vaccine for a disease that currently has none, reducing illness and death across Asia. It is applied, targeted research with a clear practical endpoint.