New mRNA Malaria Vaccine....

imhotep

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  • Mar 29, 2017
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    A new mRNA vaccine targeting immune cells in the liver could be the key to tackling malaria, a disease that causes over half a million deaths each year according to the World Health Organization, yet has no effective long-lasting vaccine.

    Trans-Tasman research collaborators from Te Herenga Waka— Victoria University of Wellington’s Ferrier Research Institute and the Malaghan Institute of Medical Research in New Zealand, and the Peter Doherty Institute for Infection and Immunity in Australia have developed an mRNA-based vaccine that can effectively target and stimulate protective immune cell responses against the malaria-causing parasite Plasmodium in preclinical models.
    The focus of the collaborative research investigating a novel target for malaria was originally on peptide-based vaccines. However, in 2018, the team shifted their approach and started investigating RNA-based vaccines – a decision that, so far, seems to have paid off with the recent success of RNA technology in vaccine development.

    “While our successful peptide-based vaccines targeting malaria only contain small protein fragments of a malaria protein, mRNA vaccines encode an entire malaria protein,” says the University of Melbourne’s Dr Lauren Holz, Research Officer at the Doherty Institute and co-author of the paper. Unlike the COVID-19 vaccine that works by neutralising antibodies, our unique approach relies on T-cells which play a critical role in immunity. Specifically, a type of T-cell called a tissue-resident memory T-cell, that halts malaria infection in the liver to completely stop the spread of infection.”

    Dr Holz says the key advantage of this vaccine is that it isn’t affected by previous exposure to malaria.

    “A lot of malaria vaccines undergoing trials have worked really well in animal models or when they’re given to people who haven’t had malaria before, but they don’t work well when given to people living in malaria-endemic regions. In contrast, our vaccine is still capable of generating protective liver-specific immune cells and providing protection even when the animal models have been pre-exposed to the disease,” says Dr Holz.

    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.