Protective liver CD8+ tissue-resident memory T cell responses induced by a novel chemo-attenuated sporozoite vaccine relies on monocyte-derived IL-15

In this study, we found that nitroquine (CI-679), used to eliminate malaria blood-stage parasites, effectively attenuated sporozoites by halting early liver-stage development. A single vaccination with CI-679-attenuated Plasmodium berghei (P. berghei) sporozoites provided significant protection to BLAB/c mice against sporozoites challenge.

The differences in protective efficacy between two genetically distinct strains, BLAB/c and C57BL/6 mice, were primarily linked to the frequency of parasite-specific CD8+ tissue-resident memory (Trm) cells. Additionally, high IL-15 expression in monocytes was associated with the generation of CD8+ Trm cells in immunized mice. Our findings characterize a novel chemo-attenuated sporozoite vaccine that warrants further human testing, and provides mechanistic evidence supporting IL-15 as an adjuvant to enhance the efficacy of exo-erythrocytic stage vaccines.