Immunization with Ty21a live oral typhoid vaccine elicits cross-reactive multifunctional CD8+ T cell responses against Salmonella enterica serovar Typhi, S. Paratyphi A and S. Paratyphi B in humans

Previously we have extensively characterized Salmonella enterica serovar Typhi (S. Typhi)-specific cell-mediated immune responses (CMI) in volunteers orally immunized with the licensed Ty21a typhoid vaccine. In this study we measured Salmonella-specific multifunctional (MF) CD8+ T cell responses to further investigate whether Ty21a elicits cross reactive CMI against S. Paratyphi A and S. Paratyphi B, which also cause enteric fever. Ty21a elicited cross-reactive CMI against all three Salmonella serotypes were predominantly observed in CD8+ T effector/memory (T(EM)) and, to a lesser extent, in CD8+CD45RA+ T(EM) (T(EMRA)) subsets. These CD8+ T cell responses were largely mediated by MF cells co producing IFN-γ, MIP-1β and expressing CD107a with or without TNF-α. Significant proportions of Salmonella-specific MF cells expressed the gut homing molecule integrin α(4)β(7). In most subjects similar MF responses were observed to S. Typhi and S. Paratyphi B, but not to S. Paratyphi A. These results suggest that Ty21a elicits MF CMI against Salmonella which could be critical in clearing the infection. Moreover, because S. Paratyphi A is a major public concern and Ty21a was shown in field studies not to afford cross-protection to S. Paratyphi A, these results will be important in developing a S. Typhi/S. Paratyphi A bivalent vaccine against enteric fevers.