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Salmonella enterica infections are an important global health problem with more than 20 million individuals suffering from enteric fever annually and more than 200’000 lethal cases per year. Although enteric fever can be treated appropriately with antibiotics, Salmonella serovars are increasingly resistant to antibiotics in highly endemic areas. Unfortunately, the currently available mono-specific vaccines against S. typhi have to be kept in an uninterrupted cold chain. Hence, the development of an effective and affordable oral vaccine against Salmonella that is not dependent on a cold chain would have a high impact on the improvement of human health in endemic areas. A new polyvalent vaccine candidate using microencapsulated S. typhi outer membrane proteins (Omps or porins) for oral administration has been developed through a collaborative project involving researchers at the Kantonsspital St. Gallen, the ETH Zürich and the Mexican Social Security Institute. The novel approach involves encapsulation of S. typhi porins in (poly(lactic-co-glycolic acid) (PLGA) microspheres, a process that grants high stability and resistance to gastric fluid. Importantly, oral application PLGA-encapsulated S. typhi porins (PESPO) elicited substantial mucosal immune responses in a pre-clinical model.