Te Herenga Waka’s trans-Tasman research collaborators – the Ferrier Research Institute at Victoria University of Wellington and the Malaghan Institute of Medical Research in New Zealand, as well as the Peter Doherty Institute for Infection and immunity in Australia have developed an mRNA-based vaccine that can effectively target and stimulate protective responses of immune cells against the parasite that causes malaria Plasmodium in preclinical models.
Professor Gavin Painter of the Ferrier Research Institute says the approach is distinctive because the team leveraged years of previous research from the University of Melbourne’s Professor Bill Heath at the Doherty Institute and Professor Ian Hermans of the Malaghan Institute .
“Thanks to this synergy, we were able to design and validate an example of an mRNA vaccine that works by generating liver-resident memory cells in a malaria model,” explains Professor Painter.
“This demonstrates the enormous potential of RNA technology to solve some of the world’s biggest health problems, as well as the growing capacity and expertise in developing mRNA vaccines here in New Zealand and Australia .”
Collaborative research into a new malaria target initially focused on peptide-based vaccines. However, in 2018 the team changed their approach and began studying RNA-based vaccines – a decision which, so far, appears to have paid off with the recent success of RNA technology in the vaccine development.
“While our malaria-targeting peptide vaccines contain only small protein fragments of a malaria protein, mRNA vaccines encode an entire malaria protein,” explains Dr Lauren Holz of the University of Melbourne , research fellow at the Doherty Institute and co-author of the study. paper.
“This is a real strength because it means we can generate a broader and hopefully more protective immune response.”
To provide additional protection, the mRNA vaccine was combined with an adjuvant – initially developed at the Malaghan and Ferrier institutes for cancer immunotherapies – which targets and stimulates specific immune cells in the liver. This additional ingredient helps localize the RNA vaccine response to the liver, a key site for preventing the parasite from growing and maturing in the body.
“When the parasite first enters the bloodstream, it travels to the liver where it grows and matures before infecting blood cells, which is when symptoms of the disease appear,” explains Dr. Mitch Ganley, postdoctoral researcher at the Ferrier Research Institute, and co-author of the study.
“Unlike the COVID-19 vaccine which works by neutralizing 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 stops malaria. liver infection to completely stop the spread of the infection.
Dr. Holz says the main advantage of this vaccine is that it is not affected by previous exposure to malaria.
“Many malaria vaccines in trials have worked very well in animal models or when given to people who have never had malaria before, but they do not work well when given to people living in areas where malaria is endemic. In contrast, our vaccine is still able to generate liver-specific protective immune cells and provide protection even when animal models have been pre-exposed to the disease,” explains the Dr. Holz.
The research team is currently working to bring the vaccine into human clinical trials, which are expected to last several years.
This research was published in Natural immunology(DOI: 10.1038/s41590-023-01562-6).
