Journal article
Jason P Mooney, Seung‐Joo Lee, Kristen L Lokken, Minelva R. Nanton, Sean-Paul Nuccio, S. McSorley, R. Tsolis
PLoS neglected tropical diseases, 2015
PLoS neglected tropical diseases, 2015
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APA
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Mooney, J. P., Lee, S. J., Lokken, K. L., Nanton, M. R., Nuccio, S.-P., McSorley, S., & Tsolis, R. (2015). Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria. PLoS Neglected Tropical Diseases.
Chicago/Turabian
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Mooney, Jason P, Seung‐Joo Lee, Kristen L Lokken, Minelva R. Nanton, Sean-Paul Nuccio, S. McSorley, and R. Tsolis. “Transient Loss of Protection Afforded by a Live Attenuated Non-Typhoidal Salmonella Vaccine in Mice Co-Infected with Malaria.” PLoS neglected tropical diseases (2015).
MLA
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Mooney, Jason P., et al. “Transient Loss of Protection Afforded by a Live Attenuated Non-Typhoidal Salmonella Vaccine in Mice Co-Infected with Malaria.” PLoS Neglected Tropical Diseases, 2015.
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@article{jason2015a,
title = {Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria},
year = {2015},
journal = {PLoS neglected tropical diseases},
author = {Mooney, Jason P and Lee, Seung‐Joo and Lokken, Kristen L and Nanton, Minelva R. and Nuccio, Sean-Paul and McSorley, S. and Tsolis, R.}
}
Abstract
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.
