Salmonella Paratyphi A outer membrane vesicles displaying Vi polysaccharide as multivalent vaccine against enteric fever


G GasperiniR AlfiniV AratoF ManciniM G ArutaP KanvatirthD PickardF NecchiA SaulO RossiF MicoliP Mastroeni 


Typhoid and paratyphoid fever have a high incidence worldwide and coexist in many geographical areas, especially in Low-Middle Income Countries (LMIC) in South and South East Asia. There is extensive consensus on the urgent need for better and affordable vaccines against systemic Salmonella infections. Generalized Modules for Membrane Antigens (GMMA), outer membrane exosomes shed by Salmonella bacteria genetically manipulated to increase blebbing, resemble the bacterial surface where protective antigens are displayed in their native environment.Here we engineered S. Paratyphi A using the pDC5-viaB plasmid to generate GMMA displaying the heterologous S. Typhi Vi antigen together with the homologous O:2 O-Antigen. The presence of both Vi and O:2 was confirmed by flow cytometry on bacterial cells and their amount was quantified on the resulting vesicles through a panel of analytical methods. When tested in mice, such GMMA induced a strong antibody response against both Vi and O:2 and these antibodies were functional in a serum bactericidal assay. Our approach yielded a bivalent vaccine candidate able to induce immune responses against different Salmonella serovars which could benefit LMIC residents and travellers.

Click here to read the article, published in the American Society for Microbiology.