The high protection of a novel chemo-attenuated sporozoite vaccine requires IL-15-mediated liver CD8+ tissue-resident memory T-cell responses
- 1Department of Pathogenic Biology, Army Medical University (Third Military Medical University), Chongqing, China
- 2Department of Clinical Laboratory, People’s Hospital of Deyang City, Deyang, China
- 3Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China
Abstract
Chemo-attenuated sporozoite vaccines (SPZ-CVacs) are considered promising for malaria prevention, but safety concerns persist regarding antimalarial drugs targeting either liver- or blood-stage parasites. In this study, we found that nitroquine (CI-679), used to eliminate malaria blood-stage parasites, effectively rendered sporozoites attenuated by arresting late liver-stage development. A single vaccination with CI-679-attenuated Plasmodium berghei (P. berghei) sporozoites conferred robust protection against sporozoite challenge in BALB/c mice. Using mouse models with distinct genetic backgrounds, we demonstrated that the robust protection conferred by the CI-679-attenuated vaccine was primarily associated with the frequency of parasite-specific CD8+ tissue-resident memory (Trm) cells mediated by IL-15. Notably, the supplement of IL-15/IL-15Ra sushi complex remarkably increased Trm frequency and improved the protective efficacy of CI-679-attenuated vaccine. Our findings characterize a novel SPZ-CVac and provide mechanistic evidence supporting IL-15 as an adjuvant to enhance the efficacy of pre-erythrocytic stage vaccines.
IMPORTANCE: Malaria remains a devastating global disease. Chemo-attenuated sporozoite vaccines show promise, yet safety concerns persist as current drugs target only liver- or blood-stage parasites. Here, we found nitroquine (CI-679) has a potentially favorable safety profile because of its dual liver- and blood-stage activity, and a single vaccination with CI-679-attenuated P. berghei sporozoites conferred robust protection against sporozoite challenge in BALB/c mice. Mechanistically, protection was associated with IL-15-mediated parasite-specific CD8+ tissue-resident memory (Trm) cells. Notably, the supplement of IL-15/IL-15Ra sushi complex remarkably increased Trm frequency and enhanced protective efficacy. Therefore, we characterize a novel chemo-attenuated sporozoite vaccine and provide mechanistic evidence supporting IL-15 as an adjuvant for pre-erythrocytic stage vaccines.
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BibTeX
@article{tan2026high,
title = {{The high protection of a novel chemo-attenuated sporozoite vaccine requires IL-15-mediated liver CD8+ tissue-resident memory T-cell responses}},
author = {Nie Tan and Chengyu Zhu and Teyang Li and Shubin Su and Shiming Jiao and Yuanli Gao and Yan Ding and Taiping Liu and Wenyue Xu},
journal = {mBio},
year = {2026},
month = sep,
doi = {10.1128/mbio.01131-26},
url = {https://doi.org/10.1128/mbio.01131-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The high protection of a novel chemo-attenuated sporozoite vaccine requires IL-15-mediated liver CD8+ tissue-resident memory T-cell responses
AU - Nie Tan
AU - Chengyu Zhu
AU - Teyang Li
AU - Shubin Su
AU - Shiming Jiao
AU - Yuanli Gao
AU - Yan Ding
AU - Taiping Liu
AU - Wenyue Xu
PY - 2026
DA - 2026/09/24
JO - mBio
DO - 10.1128/mbio.01131-26
UR - https://doi.org/10.1128/mbio.01131-26
AB - Chemo-attenuated sporozoite vaccines (SPZ-CVacs) are considered promising for malaria prevention, but safety concerns persist regarding antimalarial drugs targeting either liver- or blood-stage parasites. In this study, we found that nitroquine (CI-679), used to eliminate malaria blood-stage parasites, effectively rendered sporozoites attenuated by arresting late liver-stage development. A single vaccination with CI-679-attenuated Plasmodium berghei (P. berghei) sporozoites conferred robust protection against sporozoite challenge in BALB/c mice. Using mouse models with distinct genetic backgrounds, we demonstrated that the robust protection conferred by the CI-679-attenuated vaccine was primarily associated with the frequency of parasite-specific CD8+ tissue-resident memory (Trm) cells mediated by IL-15. Notably, the supplement of IL-15/IL-15Ra sushi complex remarkably increased Trm frequency and improved the protective efficacy of CI-679-attenuated vaccine. Our findings characterize a novel SPZ-CVac and provide mechanistic evidence supporting IL-15 as an adjuvant to enhance the efficacy of pre-erythrocytic stage vaccines. IMPORTANCE: Malaria remains a devastating global disease. Chemo-attenuated sporozoite vaccines show promise, yet safety concerns persist as current drugs target only liver- or blood-stage parasites. Here, we found nitroquine (CI-679) has a potentially favorable safety profile because of its dual liver- and blood-stage activity, and a single vaccination with CI-679-attenuated P. berghei sporozoites conferred robust protection against sporozoite challenge in BALB/c mice. Mechanistically, protection was associated with IL-15-mediated parasite-specific CD8+ tissue-resident memory (Trm) cells. Notably, the supplement of IL-15/IL-15Ra sushi complex remarkably increased Trm frequency and enhanced protective efficacy. Therefore, we characterize a novel chemo-attenuated sporozoite vaccine and provide mechanistic evidence supporting IL-15 as an adjuvant for pre-erythrocytic stage vaccines.
SN - 2150-7511
ER -