As with Salmonella Typhi, there is serious concern about increasi

As with Salmonella Typhi, there is serious concern about increasing antimicrobial resistance among Salmonella Paratyphi strains [5], [10], [12], [13], [15] and [16], underscoring the urgent need for vaccines. However, Angiogenesis inhibitor as opposed to Salmonella Typhi, there are currently no vaccines targeted against Salmonella Paratyphi in clinical use. By revisiting old data from field trials on typhoid vaccination in Chile, Levine et al. showed that the oral live Salmonella Typhi Ty21a vaccine (Ty21a), while conferring protection against typhoid fever, also conferred cross-protection against paratyphoid fever caused

by Salmonella Paratyphi B [17]. In line with this, studies by Meltzer et al. have suggested that in contrast to the parenteral Vi-capsular polysaccharide vaccine, Ty21a may confer some cross-protection against Salmonella Paratyphi A [3]. Similar results have been obtained in some other studies [18], while others have failed to confirm this [19]. Controlled OTX015 ic50 studies are needed to establish the cross-protective efficacy. As Salmonella Paratyphi is transmitted by ingestion of contaminated food or water, an effective intestinal immune response would serve as a first line of defense. The immune response

to Ty21a has been shown to consist of both mucosal and systemic humoral and cell-mediated immune responses [20], [21], [22], [23], [24], [25] and [26]. The intestinal immune response has been characterized

[20], [27], [28], [29], [30], [31] and [32] with the help of gut-derived plasmablasts. These cells are recirculating intestinal lymphocytes which have become activated upon antigen encounter, migrated to local lymph nodes and are on their way back to the intestine via lymphatics and blood [33], [34] and [35]. Catching these cells from circulation before they home back to the intestine has been used to study intestinal immune response both to oral vaccines [20] and of in enteric infections [36], [37] and [38]. The lymphocytes all carry the HR α4β7 [29] and [37], known to guide cells from the circulation into the intestinal lamina propria [33], [34], [35] and [39]. Prior to this, the approach of examining gut-originating recirculating cells has not been exploited to evaluate cross-reactive immune responses. Previous reports on the cross-protective capacity of Ty21a against paratyphoid fever appear promising as there are no vaccines available against paratyphoid fever. To examine the theoretical grounds for these reports, we investigated immunological evidence of a cross-reactive Salmonella Paratyphi-specific intestinal antibody response in enteric fever and after ingestion of the oral Ty21a (Vivotif®) vaccine. Any level of cross-protective capacity in a currently available vaccine warrants further exploration.

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