Work

Hemozoin persistence after Plasmodium infection diminishes protective whole-parasite induced CD8+ T cell responses that can be overcome by mRNA vaccination 2096

Year: 2025

Type: article

Abstract: Description Several malaria vaccine candidates, including radiation attenuated sporozoites (RAS), show disappointing performance when tested in malaria endemic regions, compared to their strong performance in malaria-naïve individuals. One hypothesis posits that prior malaria-experience alters the immune responses of individuals residing in endemic regions. Here, we developed mouse models where prior blood-stage Plasmodium exposure compromised RAS-induced CD8+ T cell responses, and ultimately compromised vaccine-mediated protection from subsequent challenge infection. Injection of mice with synthetic hemozoin phenocopied prior infection, implicating this persisting parasite-produced metabolic byproduct in poor vaccine efficacy. We found that the blood-stage-induced T cell defect could be rectified by multiple strategies, including mRNA vaccination. Moreover, a translationally relevant RAS and mRNA vaccine combination immunization enhanced Plasmodium-specific TRM formation in the liver. This newfound understanding of the role of hemozoin in modulation of T cell priming during liver-stage vaccination will be critical to design antimalarial vaccines with efficacy in malaria endemic regions. Funding Sources AI42767, AI100527, AI114543, AI167847, and AI185725 to JTH. T32AI007260 and 1F32AI174382 to MH. T32AI007260 and 1F32AI167088 to LLD. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.060