Chemoprophylaxis Vaccination with a Plasmodium Liver Stage Autophagy Mutant Affords Enhanced and Long-lasting Protection

Overview

Journal NPJ Vaccines

Date 2021 Aug 11

PMID 34376691

Citations 3

Authors

Tejram Sahu

Ella J Gehrke

Yevel Flores-Garcia

Godfree Mlambo

Julia D Romano

Isabelle Coppens

Affiliations

Soon will be listed here.

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.

Citing Articles

Whole-sporozoite malaria vaccines: where we are, where we are going.

Moita D, Prudencio M EMBO Mol Med. 2024; 16(10):2279-2289.

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Autophagy in protists and their hosts: When, how and why?.

Romano P, Akematsu T, Besteiro S, Bindschedler A, Carruthers V, Chahine Z Autophagy Rep. 2023; 2(1).

PMID: 37064813 PMC: 10104450. DOI: 10.1080/27694127.2022.2149211.

Roles of the apicoplast across the life cycles of rodent and human malaria parasites.

Buchanan H, Goodman C, McFadden G J Eukaryot Microbiol. 2022; 69(6):e12947.

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