Safety and Immunogenicity of a Trivalent Salmonella Conjugate Vaccine to S. Typhi, S. Typhimurium, and S. Enteritidis.

Abstract

Invasive disease caused by typhoid and nontyphoidal Salmonella (NTS) is a threat confronting young children in sub-Saharan Africa. We are developing a trivalent Salmonella conjugate vaccine (TSCV) consisting of typhoid Vi conjugate and core-O-polysaccharide conjugates from 2 invasive NTS serovars (S. Typhimurium and S. Enteritidis). We conducted a randomized-controlled Phase 1/2a trial assessing the safety and immunogenicity of a full-strength TSCV (FS; 25 µg of all 3 polysaccharides), half-strength TSCV (HS; 25 µg of Vi and 12.5 µg of both NTS polysaccharides), dilutional half-strength TSCV (dilHS; 12.5 µg of all 3 polysaccharides), or placebo. Local and systemic adverse events were recorded and blood was collected for serum antibody and antibody-secreting cells (ASCs). In total, 80 evaluable participants aged 20-47 years were enrolled. All vaccines were well tolerated; mild injection site pain and fatigue were the most common reactions reported. Serum antibody and ASC responses to the 3 primary polysaccharide antigens were robust, ranging between 85% and 100% response rates, with no statistically significant difference between the 3 formulations. No placebo recipients manifested significant antibody or ASC responses. These data encourage the further development of TSCV to address a pressing public health problem in young children of sub-Saharan Africa.