Next stop, cancer? How mRNA vaccines target other diseases

The epidemic has put messenger RNA (mRNA) in the spotlight.Many New Zealanders have so far received at least one of the mRNA vaccines to train their immune systems to fight Covid-19, reducing the chance of serious infection
symptoms and speeds recovery from the virus. Now, as New Zealand and Australian researchers are developing a new vaccine, mRNA technology may also hold the key to solving many other diseases, including malaria.

Globally, half a million people die from malaria every year. It is caused by a parasite called Plasmodium that infects certain species of mosquitoes, which spread the virus when they feed on humans. It travels from the skin to the liver, where it replicates and then infects red blood cells and causes symptoms. If left untreated, malaria can cause severe illness and death within 24 hours.

The new vaccine works by targeting T cells in the liver, triggering an immune response and preventing the parasite from developing and maturing.

“T cells look for pathogen-infected cells throughout the body and kill them,” said Professor Ian Hermans from Wellington’s Malahan Institute. “So they start working after infection rather than trying to prevent infection in the first place. Traditionally, it’s been quite difficult to design vaccines that specifically induce a T-cell response.”

It works in a different way than the R21/Matrix-M vaccine that the World Health Organization has just approved to prevent malaria in children and is expected to be available in some African countries next year. Demand for mRNA-based malaria vaccines is likely to be high as mosquito-borne diseases are expected to increase due to global warming.

Hermans has a background in cancer research, and until recently, much of the original work in developing mRNA vaccines was focused on this area. The new malaria vaccine contains an adjuvant, originally developed for cancer immunotherapy, that targets and stimulates liver-specific immune cells.

“It involves another cell type that I’ve been studying, called NKT cells. It’s similar to T cells, but does a slightly different job. If you think of T cells as murderous foot soldiers, NKT cells are more like loud The sergeant who shouts the orders and formulates the response. They seem to have some influence in directing the T cells to go where they are supposed to go. For malaria, we want them to be in the liver so they can kill the parasite population before it expands .”

Other malaria vaccines tend to be less effective in people who have been exposed to areas where the disease is endemic. Trials in mice showed that the new mRNA vaccine provided good protection even in those who had been previously exposed to the virus.

Now, the team is working on human trials, which are expected to take several years. “The fact that these T cells enter the liver is exciting to us because they may also play a role in liver cancer,” Hermans said. “So cancer vaccines remain a target of great interest to us.”

Cancer is a complex disease involving a large number of mutations, and it is unlikely that a preventive vaccine will be developed anytime soon. But a new generation of mRNA-based cancer treatment vaccines is on the horizon.

“They will be designed for a specific cancer and may match a specific person’s mutations, so they will be very personalized,” Herman said.

Pharmaceutical companies Moderna and Merck are currently enrolling patients in a late-stage study testing an mRNA-based skin cancer vaccine in combination with the immunotherapy drug Keytruda. The vaccine is customized for each patient, generating T cells based on the specific mutational signature of their tumor.

Other trials are studying similar cancer treatments, including colorectal, pancreatic and head and neck cancers.

More infectious diseases may also be targeted in this way. The Malahan Institute has begun investigating the potential of mRNA technology to treat hepatitis and continues to study malaria, which according to the World Health Organization, nearly half of the world’s population is at risk.

“We are sometimes asked why we do malaria research in New Zealand,” Hermans said. “With climate change, the habitats of those malaria-carrying mosquitoes may change, and who knows where they end up. So there could be a malaria problem here in the future.”