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A phase 1 randomized, placebo-controlled trial of a combination typhoid and non-typhoidal Salmonella polysaccharide conjugate vaccine

Chen, W. H.; Barnes, R. S.; Sikorski, M. J.; Datar, R.; Sukhavasi, R.; Liang, Y.; Rapaka, R. R.; Pasetti, M. F.; Sztein, M. B.; Wahid, R.; Tennant, S. M. H.; Simon, R.; Baliban, S. M.; Galen, J. E.; Lees, A.; Bernshtein, B.; Alter, G.; Ella, R.; Mohan, K.; Naidu, M. G.; Rao, D. Y.; Ella, K. M.; Levine, M. M.

2025-09-18 infectious diseases
10.1101/2025.09.15.25335795 medRxiv
Show abstract

In sub-Saharan Africa, non-typhoidal Salmonella (NTS) and Salmonella Typhi are leading causes of invasive disease among young children. Trivalent Salmonella Conjugate Vaccine (TSCV) consists of Vi capsule polysaccharide conjugated to tetanus toxoid and core-plus-O-polysaccharides from the two most prevalent invasive non-typhoidal serovars (Typhimurium, Enteritidis) conjugated to serovar- homologous flagellin subunits. We conducted a first-in-human, randomized, placebo-controlled, stepwise-dose-escalation phase 1 trial (NCT03981952) evaluating TSCV safety and immunogenicity; 22 healthy adults aged 18-45 years were randomly allocated 6.25 {micro}g TSCV (n=8), 12.5 {micro}g TSCV (n=10), or placebo (n=4). TSCV was safe and well-tolerated, with the most common solicited symptom being short- lived injection site pain. For each of the 3 polysaccharides, serum IgG and IgA ELISA antibody responses, as demonstrated by four-fold or greater increases over baseline, were observed among all vaccinees but among no placebo recipients. Binding and functional antibodies, gut-homing antibody secreting cells, and polysaccharide-specific memory B cells responses were also elicited. ClinicalTrials.gov Registry NCT03981952.

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