ArticlePLoS pathogens2025
Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination.
Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- mRNA vaccination overcomes haemozoin-mediated impairment of whole-parasite malaria vaccines in mice.Nature microbiology · 2026Article
- γδ T cell-derived IL-4 initiates CD8Nature immunology · 2026Article
- Liver sinusoid constraints make random search of CD8 T cells for Plasmodium parasites efficient.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vaccination with radiation-attenuated sporozoites (RAS) can provide highly effective protection against malaria in both humans and mice. To extend understanding of malaria immunity and inform the development of future vaccines, we studied the protective response elicited by this vaccine in C57BL/6 mice. We reveal that successive doses of Plasmodium berghei RAS favour the generation of liver CD8+ tissue-resident memory T cells (TRM cells) over circulating memory cells and markedly enhance their longevity. Importantly, RAS immunisation strongly skews the composition of the liver CD8+ TRM compartment towards cells specific for abundant sporozoite antigens, such as thrombospondin-related anonymous protein (TRAP) and circumsporozoite protein (CSP), which become major mediators of protection. The increased prevalence of sporozoite specificities is associated with limited intrahepatic attenuated parasite development and inhibition of naïve T cell responses to all parasite antigens, whether formerly encountered or not, in previously vaccinated mice. This leads to the exclusive expansion of effector T cells formed upon initial immunisation, ultimately reducing the diversity of the liver TRM pool later established. However, stronger responses to less abundant epitopes can be achieved with higher initial doses of RAS. These findings provide novel insights into the mechanisms governing malaria immunity induced by attenuated sporozoite vaccination and highlight the susceptibility of this vaccine to limitations imposed by strain-specific immunity associated with the abundant, yet highly variable sporozoite antigens CSP and TRAP.
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