The pandemic put a spotlight on messenger RNA (mRNA). By now, many New Zealanders have had at least one mRNA vaccine, to train their immune system to fight off Covid-19, reducing the chance of severe symptoms and speeding recovery from the virus. Now, mRNA technology may also be the key to tackling many other diseases, including malaria, thanks to a new vaccine being developed by New Zealand and Australian researchers.
Globally, half a million people each year die from malaria. It is caused by a parasite called plasmodium that infects certain species of mosquito, which transmit it when they feed on humans. It moves from the skin to the liver, where it replicates, before infecting red blood cells and causing symptoms. Left untreated, malaria can lead to severe illness and death within 24 hours.
The new vaccine works by targeting T-cells in the liver, which mount an immune response and prevent the parasite from developing and maturing.
“T-cells go around the body looking for cells infected by pathogens and killing them,” says Professor Ian Hermans of Wellington’s Malaghan Institute. “So, they do the job after an infection as opposed to trying to prevent it in the first place. Traditionally, it’s been quite hard to design vaccines to specifically induce T-cell responses.”
It acts in a different way to the R21/Matrix-M vaccine just approved by the World Health Organisation for the prevention of malaria in children, which is expected to be available in some African countries next year. With mosquito-borne disease predicted to rise due to global warming, there is likely to be high demand for an mRNA-based malaria vaccine.
Hermans has a background in cancer research, where a lot of the original work to develop mRNA vaccines was focused until recently. The new malaria vaccine includes an adjuvant, originally developed for cancer immunotherapies, which targets and stimulates liver-specific immune cells.
“It involves another cell-type that I had been studying, called an NKT cell. It’s like a T-cell but functions a little differently. If you imagine T-cells are the foot soldiers that do the killing, your NKT cells are more like sergeants who yell out orders and shape the response. They seem to have some influence directing the T-cells to where they should go. For malaria, we want them to be in the liver so they can kill the parasites there before they expand in number.”
Other vaccines for malaria have tended not to work as well for those people who have already been exposed in regions where the disease is endemic. Trials in mice have shown the new mRNA vaccine gives good protection even in those who have had prior exposure.
Now, the research team is working towards human trials, which they expect to take several years. “The fact these T-cells go to the liver has got us excited that maybe they could also play a role in liver cancer,” says Hermans. “So, a cancer vaccine is still very much in our sights.”
Cancer is such a complex disease involving large numbers of mutations, that it is unlikely preventive vaccines will be developed for it any time soon. But a new generation of therapeutic mRNA-based vaccines for cancer is drawing nearer.
“They will be designed for a specific cancer and probably to match a mutation a particular person has, so they’ll be very personalised,” says Herman.
Drug companies Moderna and Merck are now enrolling patients in a late-stage study testing an mRNA-based skin cancer vaccine, used in combination with the immunotherapy drug Keytruda. The vaccine is tailored for each patient to generate T-cells based on the specific mutational signature of their tumour.
Other trials are looking at similar treatments for cancers including colorectal, pancreatic, and head and neck.
More infectious diseases are also likely to be targeted this way. The Malaghan Institute has started looking at the potential of mRNA technology to treat hepatitis and is continuing work on malaria, which nearly half the world’s population is at risk of catching, according to the World Health Organisation.
“Sometimes we get asked why we do malaria research in New Zealand,” says Hermans. “With climate change, the habitat of those mosquitoes that carry malaria is likely to change and who knows where they’re going to end up. So, it’s possible there could be a malaria problem here in the future.”
