Development of a Novel mRNA-based Vaccine against Malaria

A Trans-Tasman collaboration involving New Zealand’s Te Herenga Waka — Victoria University of Wellington’s Ferrier Research Institute and the Malaghan Institute of Medical Research, along with Australia’s Peter Doherty Institute for Infection and Immunity, has developed an innovative mRNA-based vaccine against the malaria-causing parasite, Plasmodium. This breakthrough was made possible through years of cumulative research led by Professor Gavin Painter, among others.

The distinctive approach of this vaccine generates resident memory cells in the liver, crucial in combating malaria. It underscores the vast potential of RNA technology in addressing global health crises and highlights the escalating proficiency in mRNA vaccine development in Australasia.

The team originally explored peptide-based vaccines but shifted to RNA-based vaccines in 2018. This strategic redirection proved fruitful due to the recent success of RNA technology in vaccine development. Unlike peptide-based vaccines which only contain small protein fragments, the mRNA vaccines encode an entire malaria protein, allowing for a broader, more protective immune response.

Further enhancing the vaccine’s potency, it has been combined with an adjuvant developed for cancer immunotherapies. This additive targets liver-specific immune cells, localizing the RNA vaccine response to the liver, where the malaria parasite matures. This approach leverages tissue-resident memory T-cells, distinct from the neutralizing antibodies mechanism used in the COVID-19 vaccine, halting the parasite’s development in the liver to prevent infection spread.

A significant advantage of this vaccine, as highlighted by Dr. Lauren Holz, is its efficacy irrespective of previous malaria exposure. Unlike other vaccines that falter in malaria-endemic regions, this novel vaccine remains effective, generating protective liver-specific immune cells. The team’s future objective is to advance this promising vaccine into human clinical trials, a process projected to span several years.

Journal Reference:

Mitch Ganley, Lauren E. Holz, Jordan J. Minnell, Maria N. de Menezes, Olivia K. Burn, Kean Chan Yew Poa, Sarah L. Draper, Kieran English, Susanna T. S. Chan, Regan J. Anderson, Benjamin J. Compton, Andrew J. Marshall, Anton Cozijnsen, Yu Cheng Chua, Zhengyu Ge, Kathryn J. Farrand, John C. Mamum, Calvin Xu, Ian A. Cockburn, Katsuyuki Yui, Patrick Bertolino, Stephanie Gras, Jérôme Le Nours, Jamie Rossjohn, Daniel Fernandez-Ruiz, Geoffrey I. McFadden, David F. Ackerley, Gavin F. Painter, Ian F. Hermans, William R. Heath. mRNA vaccine against malaria tailored for liver-resident memory T cells. Nature Immunology, 2023; DOI: 10.1038/s41590-023-01562-6

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