Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection
Tejram Sahu,
Ella J. Gehrke,
Yevel Flores-Garcia,
Godfree Mlambo,
Julia D. Romano,
Isabelle Coppens
Affiliations
Tejram Sahu
Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health
Ella J. Gehrke
Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health
Yevel Flores-Garcia
Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health
Godfree Mlambo
Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health
Julia D. Romano
Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health
Isabelle Coppens
Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health
Abstract Genetically attenuated sporozoite vaccines can elicit long-lasting protection against malaria but pose risks of breakthrough infection. Chemoprophylaxis vaccination (CVac) has proven to be the most effective vaccine strategy against malaria. Here, we demonstrate that a liver stage-specific autophagy mutant of Plasmodium berghei (ATG8 overexpressor), when used as a live vaccine under a CVac regimen, provides superior long-lasting protection, in both inbred and outbred mice, as compared to WT-CVac. Uniquely, the protection elicited by this mutant is predominantly dependent on a CD8+ T-cell response through an IFN-γ-independent mechanism and is associated with a stable population of antigen-experienced CD8+ T cells. Jointly, our findings support the exploitation of liver-stage mutants as vaccines under a CVac protocol. This vaccination strategy is also a powerful model to study the mechanisms of protective immunity and discover new protective antigens.
