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

Mariah Hassert; Lisa L Drewry; Lecia Lynn Epping; Lisa S Hancox; Rui He; Sahaana Arumugam; Madison Mix; Aliasger K Salem; John T Harty

doi:10.1093/jimmun/vkaf283.060

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

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

Mariah Hassert, Lisa L Drewry, Lecia Lynn Epping, Lisa S Hancox, Rui He, Sahaana Arumugam, Madison Mix, Aliasger K Salem and John T Harty

The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283060

11/01/2025

DOI: 10.1093/jimmun/vkaf283.060

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Abstract

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)

Animals - Rodent Cells - T Cells Infections - Parasitic-Helminth Processes - Inflammation

Details

Title: Subtitle: Hemozoin persistence after Plasmodium infection diminishes protective whole-parasite induced CD8+ T cell responses that can be overcome by mRNA vaccination 2096
Creators: Mariah Hassert - University of Iowa
Lisa L Drewry - University of Iowa
Lecia Lynn Epping
Lisa S Hancox - University of Iowa
Rui He - University of Iowa
Sahaana Arumugam - University of Iowa
Madison Mix - University of Iowa
Aliasger K Salem - University of Iowa
John T Harty - University of Iowa
Resource Type: Abstract
Publication Details: The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283060
DOI: 10.1093/jimmun/vkaf283.060
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: Oxford University Press
Grant note: AI42767, AI100527, AI114543, AI167847, and AI185725 to JTH. T32AI007260 and 1F32AI174382 to MH. T32AI007260 and 1F32AI167088 to LLD.
Alternative title: IMMUNOLOGY2025™ Abstracts
Language: English
Date published: 11/01/2025
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Research Administration; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9985035040402771

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