World Malaria Day: SickKids Researchers uncover ‘blueprints’ for vaccine development

Researchers at The Hospital for Sick Children (SickKids) are helping to uncover the right target for a malaria vaccine by studying the proteins involved in immune responses to malaria. The team, led by Dr. Jean-Philippe Julien, Scientist in Molecular Medicine at SickKids and Canada Research Chair in Structural Immunology, recently published three separate studies that provide the molecular ‘blueprints’ for vaccine development including properties for effective and ineffective vaccine targets. These ‘blueprints’ may map how to fight the infection that kills hundreds of thousands of children every year.

Malaria is transmitted through the bite of infected Anopheles mosquitoes. In 2016, the World Health Organization (WHO) estimated that nearly half of the world’s population was at risk of malaria with 216 million cases found in 91 countries, an increase of five million cases from 2015.

The WHO’s theme for World Malaria Day (April 25) is ‘Ready to Beat Malaria’. The studies published by the Julien laboratory in collaboration with international teams contribute towards worldwide efforts for the development of an effective malaria vaccine. Julien is working to uncover sites of vulnerability on the malaria parasite and develop immunogens - the molecule responsible for eliciting an immune response - that could protect individuals against malaria and prevent further transmission. His work received a boost of support in 2017, with a $1.0 million USD grant from the PATH Malaria Vaccine Initiative and a $2.1 million USD team grant from the Bill and Melinda Gates Foundation awarded in November 2017.

“Currently there is no licensed malaria vaccine that provides long-lasting efficacy. Anti-malarial drugs exist but are too often associated with undesired side effects and resistance is building up. A vaccine has the potential to control malaria, as vaccines have done for other infectious diseases. By combining vaccination with ongoing prevention efforts in the field, the ultimate aspiration would be eradication” explains Julien.

The three studies investigated immune responses that protect against transmission and infection of the malaria parasite. The first study published in Nature Communications, described the use of a mouse model to explore new leads for the development of a malaria transmission-blocking vaccine. In the second study published in the Journal of Experimental Medicine, the team analyzed the immune response of nine volunteers who were vaccinated with a candidate vaccine and deciphered their antibody responses. In the third study published in Immunity, they described how some people living in the malaria-endemic region of Lambaréné, Gabon, make antibodies that are protective against malaria.

“Our studies revealed key sites of vulnerabilities on the malaria parasite during two life stages that are considered bottlenecks for infection and transmission. These weaknesses of the parasite had been reported to exist but had yet to be observed in high molecular detail. Our work also uncovered solutions developed by the human immune repertoire to protect against malaria and inhibit its transmission,” says Julien. “We’re using cutting-edge technology in structural biology, biophysics and protein engineering at SickKids, other Canadian centres and beyond. Our team is now designing and investigating new vaccine candidates based on insights into how human immune responses can block the life cycle of the malaria parasite.”

The team is collaborating with researchers at the German Cancer Research Center, Max Planck Institute for Infection Biology, The Scripps Research Institute, National Institutes of Allergy and Infectious Diseases, Fraunhofer USA, Sanaria Inc, the University of Tübingen, Kymab Ltd and Atreca on malaria vaccine development efforts, funded by the PATH Malaria Vaccine Initiative and the Bill and Melinda Gates Foundation. In the next 24 months, their new malaria vaccine designs will be evaluated in various pre-clinical model systems.