More time to kill: A longer liver stage increases T cell-mediated protection against pre-erythrocytic malaria

Liver stage (LS) Plasmodia mature in 2–2.5 days in rodents compared to 5–6 days in humans. Plasmodium-specific CD8+ T cell expansion differs across these varied timespans. To mimic the kinetics of CD8+ T cells of human Plasmodium infection, a two-dose challenge mouse model that achieved 4–5 days of...

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Published iniScience Vol. 26; no. 12; p. 108489
Main Authors Yadav, Naveen, Parthiban, Chaitra, Billman, Zachary P., Stone, Brad C., Watson, Felicia N., Zhou, Kevin, Olsen, Tayla M., Cruz Talavera, Irene, Seilie, Annette Mariko, Kalata, Anya C., Matsubara, Jokichi, Shears, Melanie J., Reynolds, Rebekah A., Murphy, Sean C.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 15.12.2023
Elsevier
Subjects
Biochemistry
Hepatology
Immunology
Hepatology
Biochemistry
Immunology
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Summary:Liver stage (LS) Plasmodia mature in 2–2.5 days in rodents compared to 5–6 days in humans. Plasmodium-specific CD8+ T cell expansion differs across these varied timespans. To mimic the kinetics of CD8+ T cells of human Plasmodium infection, a two-dose challenge mouse model that achieved 4–5 days of LS antigen exposure was developed. In this model, mice were inoculated with a non-protective, low dose of late-arresting, genetically attenuated sporozoites to initiate T cell activation and then re-inoculated 2–3 days later with wild-type sporozoites. Vaccines that partially protected against traditional challenge completely protected against two-dose challenge. During the challenge period, CD8+ T cell frequencies increased in the livers of two-dose challenged mice but not in traditionally challenged mice, further suggesting that this model better recapitulates kinetics of CD8+ T cell expansion in humans during the P. falciparum LS. Vaccine development and antigen discovery efforts may be aided by using the two-dose challenge strategy. [Display omitted] •Longer malaria liver stage exposure highlights the role of CD8+ T cells in protection•A two-dose challenge model in mice provides longer Plasmodium liver stage exposure•Vaccine-induced immunity is improved against the longer liver stage two-dose challenge Immunology; Hepatology; Biochemistry
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2023.108489