Modified Outer Membrane Vesicles (mOMV) as safe, effective, low cost, multivalent vaccines against typhoid and paratyphoid fever and invasive non- typhoidal Salmonella infections

The innovator award will allow us to develop a multivalent, easy to produce, low-cost, safe, effective Salmonella vaccine to be taken towards the end of preclinical experimentation. We will exploit the remarkable features of mOMV that are highly immunogenic outer membrane vesicles with self-adjuvanticity and that can be engineered for reduced reactogenicity, the latter being an important feature given that young children will be one of the target populations of vaccinees. We will engineer an attenuated strain of Salmonella Typhi, that naturally expresses the protective Vi polysaccharide antigen and the O:9 lipopolysaccharide antigen to express also the O:2 and O:4 antigens. The multivalent vaccine will therefore achieve coverage of Vi+and Vi-S. Typhi, S. Paratyphi A and a number of invasive non-typhoidal Salmonella (iNTS) strains. We will also engineer the strain to achieve reduced reactogenicity and higher yield of mOMV. In the medium/long term we will have an extremely simple and attractive vaccine to take through clinical experimentation and licensing. This will represent an innovative vaccine for travellers and residents in LMIC where different Salmonella diseases co-exist in the same geographical areas.