mRNA vaccination overcomes haemozoin-mediated impairment of whole-parasite malaria vaccines in mice

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

doi:10.1038/s41564-026-02263-0

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mRNA vaccination overcomes haemozoin-mediated impairment of whole-parasite malaria vaccines in mice

Journal article

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mRNA vaccination overcomes haemozoin-mediated impairment of whole-parasite malaria vaccines in mice

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

Nature microbiology, Vol.11(3), pp.718-730

03/2026

DOI: 10.1038/s41564-026-02263-0

PMCID: PMC12962968

PMID: 41629565

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Abstract

Immunization with radiation-attenuated sporozoites (RAS) drives effective sterilizing immunity against liver-stage Plasmodium infection. However, protection is compromised in individuals living in malaria endemic regions and the mechanisms of vaccine failure are unclear. Here we show that previous blood-stage exposure in a mouse model of Plasmodium yoelii infection compromises Plasmodium berghei RAS-induced essential CD8+ T cell responses and subsequent protection. The persisting malarial pigment haemozoin mediates impaired CD8+ T cell responses owing to impaired antigen uptake by dendritic cells, leading to reduced T cell activation. We designed a lipid nanoparticle-encapsulated mRNA vaccine that encodes a string of Plasmodium CD8+ T cell epitopes, which overcomes the defective T cell response and restores protection in Plasmodium-exposed mice. A combined RAS-plus-mRNA vaccine regimen enhances liver-resident memory T cells and protection in murine malaria-experienced hosts. The identification of haemozoin as a potential obstacle to vaccine efficacy in malaria endemic areas can inform the design of more effective malaria vaccines.

Microbiology

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: mRNA vaccination overcomes haemozoin-mediated impairment of whole-parasite malaria vaccines in mice
Creators: Mariah Hassert - University of Iowa
Lisa L. Drewry - University of Iowa
Lecia L. Pewe - University of Iowa
Lisa S. Hancox - University of Iowa
Rui He - University of Iowa
Sahaana Arumugam - University of Iowa
Madison R. Mix - University of Iowa
Aliasger K. Salem - University of Iowa
John T. Harty - University of Iowa
Resource Type: Journal article
Publication Details: Nature microbiology, Vol.11(3), pp.718-730
DOI: 10.1038/s41564-026-02263-0
PMID: 41629565
PMCID: PMC12962968
NLM abbreviation: Nat Microbiol
ISSN: 2058-5276
eISSN: 2058-5276
Publisher: NATURE PORTFOLIO
Number of pages: 27
Grant note: NIH (R21 EY034198; R21ES032937; R21 DE031042; 2P30CA086862 University of Iowa MSTP Training Grant T32 GM139776 NIH T32AI007260 and F32AI167088 NIH T32AI007260, F32AI174382, and K99 AI190129 Burroughs Wellcome Fund grant number 1051302 NIH AI42767, AI100527, AI114543, AI167847, and AI185725; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; Office of the Administrator (NIH)
Language: English
Electronic publication date: 02/02/2026
Date published: 03/2026
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: 9985139309402771

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