Multi-epitope mRNA Malaria Vaccine for Liver-Stage Specific CD8+ T Cells 3136

Sahaana Arumugam; Mariah Hassert; John T. Harty

doi:10.1093/jimmun/vkaf283.970

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Multi-epitope mRNA Malaria Vaccine for Liver-Stage Specific CD8+ T Cells 3136

Abstract

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Multi-epitope mRNA Malaria Vaccine for Liver-Stage Specific CD8+ T Cells 3136

Sahaana Arumugam, Mariah Hassert and John T. Harty

The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283970

11/01/2025

DOI: 10.1093/jimmun/vkaf283.970

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Abstract

Abstract Description Plasmodium sporozoites progress through a short obligate liver-stage, representing a critical period for vaccine targeting, prior to blood-stage infection. Malaria-specific liver tissue resident memory CD8 T cells (Trm) are critical for sterilizing immunity in mouse models of vaccination. However, the generation of liver Trm in humans remains a substantial challenge. In malaria naïve humans, multiple IV doses of radiation attenuated sporozoites (RAS) result in long-lasting sterilizing immunity. Recently, we showed that a single dose of RAS can serve as the initial priming step in a single epitope-specific prime-boost strategy of murine vaccination. The literature also suggests that CD4-derived IL-21 can contribute to the differentiation of CD8 T cells into liver-Trm. Here, we apply priming of CB6F1 mice with a low dose of RAS and boosting with recombinant Listeria monocytogenes expressing multiple malaria epitopes to generate CD8 T cell responses that can reduce liver parasite burden. To address a translationally relevant approach, RAS-primed mice were boosted with a multi-epitope malaria LNP mRNA vaccine both intravenously and intramuscularly to induce immunity. We also investigated how the addition of unconjugated aGC or a synthetic analogue 7DW8-5 to the mRNA vaccine can significantly reduce liver parasite burden and impact CD8 T cell responses. These results describe modifications of conventional RAS vaccination that address limitations of these vaccines. Funding Sources Supported by T32GM139776; T32AI007485; R01AI167847-03S1 Topic Categories Vaccines and Immunotherapy (VAC)

Animals - Rodent Cells - T Cells Infections - Parasitic-Helminth Molecules - Adhesion Molecules Processes - Memory

Details

Title: Subtitle: Multi-epitope mRNA Malaria Vaccine for Liver-Stage Specific CD8+ T Cells 3136
Creators: Sahaana Arumugam - University of Iowa
Mariah Hassert - University of Iowa
John T. Harty - University of Iowa
Resource Type: Abstract
Publication Details: The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283970
DOI: 10.1093/jimmun/vkaf283.970
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: Oxford University Press
Grant note: Supported by T32GM139776; T32AI007485; R01AI167847-03S1
Alternative title: IMMUNOLOGY2025™ Abstracts
Language: English
Date published: 11/01/2025
Academic Unit: Pathology
Record Identifier: 9985035035202771

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