A new type of malaria vaccine could beat all strains

JENNIFER REIMAN, GRIFFITH UNIVERSITY

A new type of malaria vaccine that has been shown to be safe in mice is about to start trials in humans.

This promising vaccine is different to other approaches to stopping the deadly disease because we use the whole malaria parasite in it. And it is able to protect against multiple strains of the illness.

Malaria and the need for a vaccine

Malaria is a mosquito-borne disease infecting nearly 250 million people each year across 109 countries. It causes approximately one million deaths each year, mostly among African children under the age of five.

The parasite has a complex life cycle with half of it lived within the female mosquito, and the other half in the human host (first within the liver and then by infecting red blood cells).

When the parasite bursts out of infected red blood cells, it destroys the cells and causes the symptoms of malaria.

Current preventive measures against malaria include those that act on the mosquito including insecticide-treated bed nets (physical barrier) and indoor residual spraying of chemicals (insecticides) to kill mosquitoes when they land on the walls.

If you’re infected, anti-malaria drugs (artemisinin-based combination therapies) are used to kill the parasite, but not everyone has access to them.

What’s more, mosquitoes and malaria parasites are continually developing resistance to current chemicals and drugs, frustrating efforts to protect against the illness.

There is no licensed vaccine against malaria, and the most advanced experimental one in clinical trials, RTS,S is showing little protection.

Our vaccine

Researchers around the world have been working on a vaccine for malaria for over 80 years. The team I’m in has been working on the problem for over 20 years.

Based on previous results from our group showing that a vaccine containing low doses of the dead parasite protected against malaria, we decided to use the whole parasite while it is still inside the red blood cell (the second stage of malaria infection) in our vaccine.

Colleagues in North America had previously showed that treating sporozoites (the malaria parasite at the stage when it is transmitted from an infected mosquito) with a particular drug protected against infection with sporozoites of all strains.

We used this same drug to treat infected red blood cells. The drug binds to the parasite’s DNA and prevents it from multiplying.

We treated red blood cells from mice infected with malaria with the drug in a test tube, then washed away the excess drug and gave the remaining treated cells to mice. This is our vaccine.

Later, we infected the mice with malaria to see if they were protected. We found that mice given our vaccine before infection did not develop as many parasites in their blood. Some of the mice had so few parasites that we were unable to see them when we looked at the blood under a microscope.

And even though mice were immunised with only one strain of malaria and infected with a different strain, they were also protected by our vaccine. That means that our vaccine protects against all strains of malaria.

How our vaccine is different

Previous vaccines have been able to activate humoral immunity (protection mediated by antibodies). These vaccines stimulate to body to make antibodies that bind to proteins on the surface of the parasite and can prevent parasites from invading new red blood cells. Or they can make antibodies that bind to the surface of infected red blood cells and are important in their removal.

These vaccines have, for the most part, not been successful. Malaria can hide from these antibodies by making a new version of the protein that won’t be recognised by the antibodies.

People who live in malaria infected areas do eventually develop protection against malaria symptoms. But this protection doesn’t occur until they have been infected with multiple strains of malaria (and only if they don’t die from one of the infections first).

Unlike naturally acquired immunity to malaria, our vaccine works by turning on cell-mediated immunity which involves T lymphocytes (a type of white blood cell). These T lymphocytes are able to recognise all kinds of proteins including those hidden inside the malaria parasite.

The hidden proteins may be shared between the various strains of malaria and we suspect that’s why our vaccine protects not only against the strain given in the vaccine but all strains of malaria.

The next steps

The results from our studies in mice has prompted us to test our malaria vaccine in humans. Within the next few months, we will begin a human clinical trial testing the vaccine made in human red blood cells that are infected with the human malaria parasite.

If results of the study in healthy Australian volunteers is promising, the vaccine will progress onto studies in areas where malaria is present. We are very encouraged by the results so far and optimistic that our vaccine approach will aid the fight against this debilitating illness that affects so many people around the world.