Lack of Immune Response to the Vi Component of a Vi-Positive Variant of the Salmonella typhi Live Oral Vaccine Strain Ty21a in Human Studies

Abstract

New typhoid vaccines have been sought to replace the reactogenic parenteral whole cell vaccines. Both Ty21a, a live oral attenuated Vi-negative Salmonella typhi vaccine strain, and parenteral Vi polysaccharide vaccine are safe and efficacious in field trials. Toachieve potentially greater protective efficacy, a derivative of Ty21a that expresses Vi polysaccharide was prepared and its safety and immunogenicity assessed in 27 adult volunteers. The volunteers received either one dose of 5 × 10⁵, 5 × 10⁷, or 5 × 10⁹ cfu or three doses of 5 × 10⁹ cfu of lyophilized vaccine and were observed for adverse effects on a research isolation ward. The vaccine was well tolerated; however, at the highest dose, 13% of volunteers had mild diarrhea. Serial blood cultures were negative for the vaccine strain. Vaccinewas shed in the stool of most volunteers at the higher doses for 1–4 days. No serum antibodies to Vi, circulating cells secreting antibody to Vi, or jejunal fluid antibodies to Vi were detected in any volunteer.