MRNA vaccination overcomes hemozoin-mediated impairment of whole parasite vaccine efficacy for malaria.

ABSTRACT: Malaria is a persistent global public health threat. Immunization with Radiation Attenuated Sporozoites (RAS) drives efficient CD8+ T cell dependent sterilizing immunity to malaria in humans. However, this protection is compromised in individuals living in malaria endemic regions and the mechanism(s) of the vaccine failure remain incompletely understood. In this study, we develop a murine model of Plasmodium infection where prior blood-stage exposure compromises RAS-induced CD8+ T cell responses and subsequent protection. We further identify the persisting malarial pigment hemozoin as a mediator of impaired CD8+ T cell responses. Mechanistically, we link this defect to impaired antigen uptake by dendritic cells, leading to reduced T cell activation. Importantly, we designed a lipid

SUBMITTER: Hassert M 

PROVIDER: S-EPMC12636498 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature