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On World Malaria Day, we spotlight the relentless efforts of researchers at the Doherty Institute, in pursuit of knowledge, with each discovery bringing us a step closer to eliminating malaria.

From the shores of Papua New Guinea to the laboratories in Melbourne, cross-disciplinary researchers unite in the fight against a life-threatening disease that infected 249 million people worldwide in 2022.

Read on for an overview of the research done at the Doherty Institute to combat malaria.

Slowing down malaria parasites’ biological clock to slow the spread of the disease

University of Melbourne’s Associate Professor Ashraful Haque, a Lab Head and a Lead for the Bacterial and Parasitic Infections theme at the Doherty Institute, was one of the first to define mechanisms of immune-suppression during malaria. In a paper recently published in mBio, Professor Haque shed light on the biological clock of the Plasmodium parasites, the pathogens causing malaria. He found that these tiny parasites operate like clockwork within the bloodstream, replicating in sync with the body's day-night cycle. They use the body's natural rhythms to their advantage, multiplying and spreading their harmful effects.

Professor Haque and his team made a fascinating discovery which could help stop the disease in its tracks. They found that the body's inflammatory response changes blood composition, making the environment less hospitable for the parasites, therefore hindering parasite reproduction. This significant finding could possibly inform the development of a new strategy for preventing or limiting severe disease. Indeed, stretching the parasites’ biological clock could provide crucial time for medical teams to administer life-saving drugs.

Advancing malaria treatment through immune targets and drug development

University of Melbourne’s Dr Michael Duffy, Senior Research Fellow at the Doherty Institute, aims to identify immune targets in severe malaria and the proteins that the parasite uses to activate its genes, all in pursuit of developing vaccines and drugs.

Together with collaborators from the Doherty Institute and Indonesia, Dr Duffy found genes used by the parasites that cause severe disease, including a family of proteins that the parasites switch between to evade the immune system. The researchers went on to investigate the immunity to the “disguises” used by the parasites (Priyanka, 2023; Rambhatla, 2022; Duffy, 2016).

People living in malaria-endemic regions become immune to severe malaria disease in childhood. Dr Duffy is now working with colleagues in Ghana to investigate which of these protein “disguises” elicit immunity associated with protection from severe malaria disease, and whether they could be used for vaccine development.

He also studies the proteins used by malaria parasites to activate and silence their genes. He is currently developing methods to identify molecules targeting these proteins and killing the parasites, offering promising avenues for malaria treatment.

Research into liver-stage immunity leads to innovation in malaria vaccine design

The Heath lab specialises in understanding how the immune system controls malaria during the liver stage of infection. The team’s research has revealed that a subset of T cells, termed resident memory T cells (TRM), are crucial for killing malaria parasites as they replicate in liver cells.

Their aim is to uncover the biological pathways that lead to the formation of liver TRM cells, and then to use this knowledge to develop methods to enhance their generation in next-generation vaccines.

In a recent study published in Nature Immunology, the researchers showed modifying a standard mRNA vaccine with a substance that activates certain types of immune cells can effectively generate liver TRM cells and protect against malaria challenge in a murine model. Their goal is to advance this type of approach for testing in humans.

Immune cell interaction with immune boosting molecules opens avenues for new vaccine development

University of Melbourne’s Dr Lynette Beattie, Senior Research Officer at the Doherty Institute, also focuses on the immune response to the liver stage of malaria infection, with a particular interest on host-pathogen interactions.

For a while now, scientists have understood that a specific group of cells called 'gamma delta T cells' play a crucial role in building immunity against liver-stage malaria. This is especially true when immunity is induced via injection of attenuated parasites.

In a fascinating discovery, Dr Beattie and her team recently found that gamma delta T cells play a vital role because they rapidly release two specific immune-boosting molecules: 'interleukin-4' and 'interferon-gamma'. This finding was surprising because these molecules are typically thought to have opposite effects. However, in this case, they work together synergistically. The researchers are now investigating this process in more detail to determine see if these two immune-boosting molecules could be used to enhance the immune response in the context of vaccination.

Tackling placental malaria to protect mothers and babies

In the tropical landscapes of Papua New Guinea, placental malaria poses a grave threat to pregnant women and their unborn babies.

 Led by University of Melbourne’s Professor Stephen Rogerson and Dr Elizabeth Aitken at the Doherty Institute, researchers are hunting for antibodies that can inhibit the parasite from binding to the placenta, preventing complications like miscarriages and stillbirths.

Through innovative research in collaboration with other experts at the Doherty Institute, the team aims to develop lab-made antibodies capable of thwarting placental infection. By targeting specific proteins crucial for parasite binding, they seek to disrupt this interaction and aid the immune system in clearing the infection.

By studying the intricate details of these antibodies, the researchers hope to develop effective treatments against placental malaria, potentially saving lives and alleviating the burden of the disease.