ABSTRACT
The attenuation and immunogenicity of two novel
Salmonella
vaccine strains,
Salmonella enterica
serovar Typhi (Ty2 Δ
aroC
Δ
ssaV
, designated ZH9) and
S. enterica
serovar Typhimurium (TML Δ
aroC
Δ
ssaV
, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 10
7
, 10
8
, or 10
9
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 10
8
and two of three receiving 10
9
CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 10
8
and 10
9
CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 10
9
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.