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Medientyp:
E-Artikel
Titel:
Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection
Beteiligte:
Sahu, Tejram;
Gehrke, Ella J.;
Flores-Garcia, Yevel;
Mlambo, Godfree;
Romano, Julia D.;
Coppens, Isabelle
Erschienen:
Springer Science and Business Media LLC, 2021
Erschienen in:
npj Vaccines, 6 (2021) 1
Sprache:
Englisch
DOI:
10.1038/s41541-021-00360-1
ISSN:
2059-0105
Entstehung:
Anmerkungen:
Beschreibung:
AbstractGenetically 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 ofPlasmodium 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.