Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

In immunocompetent individuals,non-typhoidal salmonella serovars (nts) are associated with gastroenteritis,however,there is currently an epidemic of nts bloodstream infections in sub-saharan africa. plasmodium falciparum malaria is an important risk factor for invasive nts bloodstream in african children. here we investigated whether a live,attenuated salmonella vaccine could be protective in mice,in the setting of concurrent malaria. surprisingly,mice acutely infected with the nonlethal malaria parasite plasmodium yoelii 17xnl exhibited a profound loss of protective immunity to nts,but vaccine-mediated protection was restored after resolution of malaria. absence of protective immunity during acute malaria correlated with maintenance of antibodies to nts,but a marked reduction in effector capability of salmonella-specific cd4 and cd8 t cells. further,increased expression of the inhibitory molecule pd1 was identified on memory cd4 t cells induced by vaccination. blockade of il-10 restored protection against s. typhimurium,without restoring cd4 t cell effector function. simultaneous blockade of ctla-4,lag3,and pdl1 restored ifn-γ production by vaccine-induced memory cd4 t cells but was not sufficient to restore protection. together,these data demonstrate that malaria parasite infection induces a temporary loss of an established adaptive immune response via multiple mechanisms,and suggest that in the setting of acute malaria,protection against nts mediated by live vaccines may be interrupted. © 2015 mooney et al.