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

Autor: Naveen Yadav, Chaitra Parthiban, Zachary P. Billman, Brad C. Stone, Felicia N. Watson, Kevin Zhou, Tayla M. Olsen, Irene Cruz Talavera, Annette Mariko Seilie, Anya C. Kalata, Jokichi Matsubara, Melanie J. Shears, Rebekah A. Reynolds, Sean C. Murphy
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: iScience, Vol 26, Iss 12, Pp 108489- (2023)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2023.108489
Popis: 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.
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