Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

Evaluation of oral live attenuated Salmonella typhi and Salmonella typhimurium vaccines. A new live oral vaccine for typhoid fever.

We have studied the immunization of healthy volunteers with novel oral attenuated Salmonella typhi and S. typhimurium vaccine strains harbouring defined combined aroC and type III secretion (ssaV) mutations. In particular, the attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 Delta aroC Delta ssaV, designated ZH9) and S. enterica serovar Typhimurium (TML Delta aroC Delta ssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 107, 108, or 109 CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool.

Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 108 and two of three receiving 109 CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 108 and 109 CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 109 CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable.

These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.

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Reported by

St George's Hospital Medical School
75724 London
United Kingdom
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