In patients with primary infection, the median (min–max) of the number (/106 PBMC) of ASC (IgA + IgG + IgM) was 241 (175–613) for those specific to Salmonella Typhi, 85 (32–225) to Paratyphi A, 30 (24–133) to Paratyphi B and 8 (6–10) to Paratyphi C ( Fig. 3A). In the patient with the relapse, the numbers of ASC were 28, 14, 28 and 4/106 PBMC, respectively ( Fig. 3 B). In the patient with a Salmonella Paratyphi A infection, the respective numbers were 13, 23, 19 and 0/106 PBMC, with no response to Salmonella Egusi ( Fig. 3C). The

expressions of HR (mean ± SD) on Salmonella Typhi – and Salmonella RAD001 Paratyphi B-specific ASC in the vaccinees are shown in Fig. 4. Almost all of the ASC expressed the intestinal HR, α4β7-integrin (95 ± 5% to Salmonella Typhi and 97 ± 6% to Salmonella Paratyphi B), while the peripheral lymph node HR, l-selectin, and the cutaneous HR, CLA, were found on smaller proportions of them (27 ± 17% and 0.4 ± 1% to Salmonella Typhi and 49 ± 18% and 7 ± 8% to Salmonella Paratyphi B, respectively). The expressions of HR on pathogen-specific ASC in patients with enteric fever are shown in Fig. 4. Almost all ASC expressed α4β7-integrin (92 ± 7%), while l-selectin and CLA were expressed less frequently (50 ± 25% and 8 ± 10%), Roxadustat thus resembling the HR-profile of the Salmonella Typhi- and Paratyphi B-specific responses in vaccinees in this and previous studies [18] and [31]. There are no vaccines

against paratyphoid fever in clinical use. This study presents immunological evidence supporting studies that have previously reported the potential of Ty21a vaccine to protect against paratyphoid fever. There

are four studies evaluating the protective efficacy of either Ty21a or the old parenteral whole cell vaccine (no longer in use) against Salmonella Paratyphi A. Two of these report protection [3] and [18] and two of them do not [19] and [41]. In a study in travelers to Nepal, the majority of those immunized with a whole-cell parenteral vaccine and some Rolziracetam with Ty21a, Schwartz et al. estimated an overall efficacy of 95% against Salmonella Typhi and 72–75% against Salmonella Paratyphi A [18]. Meltzer et al. evaluated imported cases of enteric fever in Israeli travelers to India in an observational study. Travellers were immunized with Ty21a until 2001 and after that with parenteral Vi-polysaccharide vaccine. The general attack rate by Salmonella Paratyphi A was 0.26 in 10,000 during Ty21a and 0.79 during Vi-vaccination. Thus, Ty21a was suggested to confer some protection against Salmonella Paratyphi A [3]. In contrast to these studies, in a large field trial in Plaju, Indonesia, Ty21a was not found to protect against paratyphoid A [19]. However, in that study three doses of Ty21a were administered at an interval of seven instead of two days between doses, leading also to a poor protective efficacy of only 42% against typhoid fever.