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

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.

• Authors: Jason P Mooney, Seung-Joo Lee, Kristen L Lokken, Minelva R Nanton, Sean-Paul Nuccio, Stephen J McSorley, Renée M Tsolis
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 9 Issue 9 Pg. e0004027 ( 2015) ISSN: 1935-2735 [Electronic] United States
• PMID: 26366739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Bacterial
• Salmonella Vaccines
• Vaccines, Attenuated

Topics

• Animals
• Antibodies, Bacterial (blood)
• Bacteremia (complications, immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Disease Models, Animal
• Female
• Immune Tolerance
• Malaria (complications, immunology)
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Salmonella Infections, Animal (complications, immunology)
• Salmonella Vaccines (immunology)
• Vaccines, Attenuated (immunology)