LAUSR

Salmonella Typhi is the causative agent of typhoid fever in humans, responsible for approximately 21 million infections and 222,000 deaths globally each year. The current licensed vaccines provide moderate protection to recipients aged >2 years. Prior work on typhoid vaccines has focused on injectable Vi capsular polysaccharide or Vi–protein conjugates and live, oral attenuated S. Typhi vaccines to induce humoral anti-Vi antibodies, while the value and importance of anti-O9 antibodies is less well established. In this study, we constructed a S. Typhimurium strain that synthesizes Vi capsular antigen in vivo and produces the immunodominant O9-antigen polysaccharide instead of its native O4-antigen. The live recombinant attenuated S. Typhimurium mutants were effective in stimulating anti-Vi and anti-O9 antibodies in a mouse model, and the surface Vi capsular expression did not affect the immune responses against the O9 O-antigen polysaccharide. Moreover, the resulting anti-Vi and anti-O9 antibodies were effective at killing S. Typhi and other Salmonella spp. expressing Vi or O9 antigen polysaccharides and provided efficient protection against lethal challenge by S. Typhimurium and S. Enteritidis. Our work highlights the strategy of developing live attenuated S. Typhimurium vaccines to prevent typhoid fever by targeting the both Vi capsular and O9 O-polysaccharide antigens simultaneously.Typhoid fever: Turning Salmonella bacteria against each otherAn attenuated strain of modified Salmonella Typhimurium bacteria could answer calls for a more effective typhoid fever vaccine. Current vaccines against typhoid-causing Salmonella Typhi are only moderately effective and potentially ineffective in children under 5 years. Qingke Kong and Roy Curtiss, leading a team of US and Chinese researchers, developed an attenuated version of the less-pathogenic S. Typhimurium that, when orally dosed in mice, expresses bacterial sugar-chain molecules known to elicit a strong immune response. In an in vitro assay, the antibodies produced by the mice in response to these molecules killed S. Typhi and related Salmonella bacteria with similar surface molecules, indicating a potential cross-protective ability. Further research would reveal whether this two-pronged live vaccine has the potential to protect in vivo, in live animals and in humans.