Abstract
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.
Highlights
Typhoid fever is a systemic infection in humans caused by Salmonella enterica subsp. enterica serovar Typhi
Typhoid fever outbreaks are frequently reported in Sub-Saharan Africa, Southeast Asia, and other developing countries, with infants, children, and adolescents being the most commonly infected
Most typhoid fever cases occur among travelers returning from typhoid-endemic areas.[3]
Summary
Typhoid fever is a systemic infection in humans caused by Salmonella enterica subsp. enterica serovar Typhi Typhoid fever is a systemic infection in humans caused by Salmonella enterica subsp. Typhi), with symptoms of fever, chills, respiratory distress, and abdominal pain, which are often non-specific and clinically indistinguishable from other febrile illnesses.[1] the first inactivated S. Typhi vaccine was licensed >100 years ago, typhoid fever remains a major public health concern with high mortality and morbidity worldwide. The global burden of typhoid fever estimated was approximately 21 million infections and 222,000 deaths annually.[2] Typhoid fever outbreaks are frequently reported in Sub-Saharan Africa, Southeast Asia, and other developing countries, with infants, children, and adolescents being the most commonly infected. The emergence of antibiotic resistance in clinical isolates of S. Typhi has resulted in typhoid fever being increasingly difficult to treat.[4] In the short term, vaccination is the most effective and economic method to prevent this disease
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