The high protection of a novel chemo-attenuated sporozoite vaccine requires IL-15-mediated liver CD8(+) tissue-resident memory T-cell responses.

A single dose of CI-679-attenuated Plasmodium berghei sporozoites induces IL-15-dependent liver CD8(+) tissue-resident memory T cells, achieving robust malaria protection in mice.

• Why it matters: Malaria remains a major global health challenge, and current chemo-attenuated vaccines face safety concerns due to limited targeting of parasite stages. Enhancing vaccine efficacy while ensuring safety is critical for effective malaria prevention.
• What they did: Researchers developed a novel chemo-attenuated sporozoite vaccine using nitroquine (CI-679), which arrests late liver-stage development, and tested its protective capacity in mouse models. They examined immune responses, focusing on IL-15's role in CD8(+) tissue-resident memory T-cell induction.
• The result: The vaccine provided strong protection linked to IL-15-mediated Trm cells, and supplementing IL-15/IL-15Ra complexes further increased Trm frequency and vaccine efficacy, highlighting IL-15 as a promising adjuvant for malaria vaccines.