Towards a non-living vaccine for shigellosis

Abstract

Shigellosis is an acute invasive enteric infection caused by Shigella spp. with an incidence of 165 millions episodes leading to 1.1 millions deaths. Considering bacteria easily spread from person to person and the emergence of multidrug- resistant Shigella strains, WHO gave high priority for the development of a shigellosis vaccine in 1991. Unfortunately, none of the proposals have an acceptable success. On this context, our proposal is based of the employment of an acellular vaccine for mucosal administration, containing relevant antigens from Shigella. Moreover, in order to increase its efficacy, it was propose the use of nanoparticles as adjuvants. Considering pathogenesis of Shigella, we select outer membrane vesicles (OMVs) as the subcellular extract. Since they are part of the outer membrane of bacteria, OMV extraction seems to be a effective strategy for isolation of the most relevant antigens of bacteria. Nevertheless, safety of this kind of subcellular vaccines is usually hampered with a lower inherent immunogenicity. Consequently, in order to obtain an adequate immune response and obtain a delivery system that allow mucosal administration, the antigenic extract from Shigella would be encapsulated in Gantrez® AN, a copolymer of ether and maleic anhydride (PMV/MA) with bioadhesive properties.