Intestinal immunity is elicited within a week and previous doses in this schedule may act against the last two doses, as shown in studies focusing on dosing intervals of Ty21a [27] and [28]. Hence, it could be argued that only one effective dose was administered in that study. The lack of cross-protection has also been suggested to be due to a particularly high incidence of the disease at that trial venue [17]: protection provided by inactivated whole-cell parenteral typhoid vaccines can be insufficient if the challenge inoculum is high enough [42]. In Thailand, Bodhidatta et al. [41] reported a decrease in Salmonella Typhi- but not Salmonella

Paratyphi A-positive blood cultures during a typhoid fever epidemic after introduction of parenteral whole cell typhoid vaccine in the national vaccination program. Anticancer Compound Library supplier However, it was a retrospective study with no control groups and the number of Salmonella Paratyphoid A cases remained low throughout the study. Hence there are several studies, none of which was originally planned to answer this question, and the results remain somewhat contentious. As to the cross-protection against Salmonella Paratyphi Bcl-2 inhibitor B, Levine et al. [17] re-analyzed pooled data from two large field trials they had carried out in Chile: Ty21a, while conferring

58% protection against typhoid fever, was also found to confer 49% protection against paratyphoid B fever. The numbers of paratyphoid Isotretinoin A cases were too low to allow an analysis of efficacy against this pathogen. The immunological background accounting for the cross-protection elicited by Ty21a against paratyphoid fever has been suggested to be

based on shared epitopes among the O antigens [5], [17] and [18]. Ty21a and Salmonella Typhi both carry O-9,12, Salmonella Paratyphi A carries O-1,2,12, Salmonella Paratyphi B O-1,4,5,12, Salmonella Paratyphi C O-6,7 and Salmonella Egusi O-41 antigens. Hence, both Salmonella Paratyphi A and B share the O-12 epitope with Salmonella Typhi and Ty21a. Consistent with this, in the present study Ty21a induced a significant cross-reactive immune response to Salmonella Paratyphi A and B but not to Salmonella Paratyphi C or Salmonella Egusi (no O-antigens shared). Notably Salmonella Paratyphi C shares the Vi-capsular polysaccharide with Salmonella Typhi, while Ty21a lacks this structure. Presumably, Vi-capsular polysaccharide vaccine could confer protection against Salmonella Paratyphi C, which, however, represents only a rare cause of enteric fever. The small numbers of plasmablasts reactive with Salmonella Paratyphi C in six Ty21a-vaccinated volunteers in this study are presumably due to some minor antigens present when whole bacteria were used as antigens. While the present study shows a cross-reactive intestinal humoral response, others have shown cross-reactive cell-mediated responses [22]: Tagliabue et al.