mRNA vaccine against malaria tailored for liver-resident memory T cells.
Mitch GanleyLauren E HolzJordan J MinnellMaria N de MenezesOlivia K BurnKean Chan Yew PoaSarah L DraperKieran EnglishSusanna T S ChanRegan J AndersonBenjamin J ComptonAndrew J MarshallAnton CozijnsenYu Cheng ChuaZhengyu GeKathryn J FarrandJohn C MamumCalvin XuIan A CockburnKatsuyuki YuiPatrick BertolinoStephanie GrasJérôme Le NoursJamie RossjohnDaniel Fernandez-RuizGeoffrey I McFaddenDavid F AckerleyGavin A PainterIan F HermansWilliam R HeathPublished in: Nature immunology (2023)
Malaria is caused by Plasmodium species transmitted by Anopheles mosquitoes. Following a mosquito bite, Plasmodium sporozoites migrate from skin to liver, where extensive replication occurs, emerging later as merozoites that can infect red blood cells and cause symptoms of disease. As liver tissue-resident memory T cells (Trm cells) have recently been shown to control liver-stage infections, we embarked on a messenger RNA (mRNA)-based vaccine strategy to induce liver Trm cells to prevent malaria. Although a standard mRNA vaccine was unable to generate liver Trm or protect against challenge with Plasmodium berghei sporozoites in mice, addition of an agonist that recruits T cell help from type I natural killer T cells under mRNA-vaccination conditions resulted in significant generation of liver Trm cells and effective protection. Moreover, whereas previous exposure of mice to blood-stage infection impaired traditional vaccines based on attenuated sporozoites, mRNA vaccination was unaffected, underlining the potential for such a rational mRNA-based strategy in malaria-endemic regions.
Keyphrases
- plasmodium falciparum
- induced apoptosis
- cell cycle arrest
- binding protein
- patient safety
- cell death
- risk assessment
- signaling pathway
- climate change
- oxidative stress
- metabolic syndrome
- adipose tissue
- insulin resistance
- skeletal muscle
- endoplasmic reticulum stress
- high fat diet induced
- depressive symptoms
- pi k akt
- wound healing