gms | German Medical Science

Malaria remains one of the most important infectious diseases and an effective vaccine does still not exist. Sterile protection against Plasmodium challenge can be achieved by immunization with radiation attenuated sporozoites (RAS) in mice and man. More recently, genetically attenuated parasites (GAP) have been developed that are arrested at a defined time point during liver stage development and confer immunity similar to RAS. GAP vaccination has proven highly efficacious, eliciting sterile protection against Plasmodium challenge in a CD8 T-cell dependent manner.

Concurrent infection with other pathogens generates immune responses that could interfere with memory T-cell responses elicited upon vaccination and thus impair protection. Malaria endemic areas also see high prevalences of tuberculosis (Tb) caused by Mycobacterium tuberculosis (Mtb). A strong impact of concurrent mycobacteria infection with the attenuated vaccine strain BCG on RAS-mediated protection has been demonstrated already more than 30 years ago.

We here present a study examining the influence of Mtb infection on vaccination with P. berghei uis3^-/-GAP. We found a slight increase in susceptibility to blood-stage infection after wildtypesporozoite challenge in C57BL/6 mice that had been co-infected with Mtb after, but not before 3 immunizations with GAP. This trend was confirmed by evaluation of the parasite liver burden, which is significantly elevated in Mtb post-infected mice. Abrogation of protection cannot be ascribed to a change in the cytokine milieu during liver stage infection, as levels of IFNγ, TNFα, IL-10 and further cytokines remain unaffected in acutely co-infected animals. These data indicate that mycobacterial infection hampers vaccination with live-attenuated sporozoite malaria vaccines. Given the high prevalence of Mtb infections and the wide use of BCG live vaccine in malaria endemic areas, this has major implications on whole-sporozoite malaria vaccination.