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Videos unlock malaria mystery

Burnet Institute

17 July, 2019

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Image: Burnet's Head of Cell Imaging, Dr Paul Gilson prepares videos of malaria parasite invasion

Hi-tech videos by Burnet Institute scientists of malaria parasite invasion have validated important discoveries by Oxford University for the potential development of a world-first effective malaria vaccine.

The Oxford research, published in the prestigious journal, Cell, identifies how a protein called RH5 helps human antibodies to block Plasmodium falciparum malaria from invading and destroying red blood cells.

The collaborative study also identifies a new antibody that slows down the speed with which RH5 binds to red blood cells, giving antibodies that block RH5 more time to act, helping them become more effective.

But the journal agreed to publish only after the addition of microscopic live video recordings by Burnet researchers, which verified the impact of RH5.

“The Oxford team had spent years gathering all this beautiful information and gone to the journal with this hypothesis about the protein’s role in helping to slow down the invasion process, but they couldn’t show that was actually the case,” study co-author, Dr Paul Gilson, Burnet’s Head of Cell Imaging, said.

“So they asked us for video data to substantiate their research, and it was almost too good to be true when we did the work and got the data, it showed they were spot on.

“Then the Oxford team said we need to blind all the antibodies so you don’t know what they are and go back and repeat it all.

“So they sent us some antibody cocktails, and from being able to observe in real time how long the various evasion stages were taking, we were able to predict perfectly what the antibody combinations were.

“We were excited, and I think they were pretty happy. They resubmitted the paper and the journal reconsidered it and it was accepted. The video proved their hypothesis.”

Study co-author, Burnet Director and CEO, Professor Brendan Crabb AC said it had been widely speculated that the effectiveness of experimental vaccines was being undermined by the speed at which the parasite invades, which was too fast for antibodies generated by the vaccine to intervene.

“We now know that this idea is indeed quite likely, and not only that, but we have a tool to slow invasion so that protective antibodies can work effectively,” Professor Crabb said.

Burnet’s role in this study took more than 12 months to complete, and involved the training of a post-doctoral scientist, Dr Rasika Kumarasingha, to shoot the videos.

Dr Gilson said the malaria parasite is well suited to research using live cell imaging.

“The challenge is keeping the cells alive on the microscope, which sits in a box, it’s heated up to body temperature and we supply it with all the gases and humidity that the cells need,” he said.

“Watching things happen in real time can tell you a lot of information rather than inferring it from biochemical assays, so the two marry together pretty well.

“And there are plenty of other vaccine targets out there whose antibodies to the parasite proteins we could understand more clearly if we could visualise what was going on.”

Dr Gilson said the research could help to inform the development of a much-needed highly effective vaccine for malaria, which, according to the World Health Organization (WHO), caused 435,000 deaths in 2017 – mainly young children – from more than 219 million cases globally.

A vaccine is fundamental to achieving WHO’s Global Elimination Target of a 90 percent reduction in malaria incidence and mortality globally by 2030.

This work was done in collaboration with researchers at the Center for Global Infectious Disease Research at the Seattle Children’s Research Institute (USA), Laboratory of Malaria and Vector Research (USA), Cell Surface Signalling Laboratory at the Wellcome Trust Sanger Institute (Cambridge), and ExpreS2ion Biotechnologies (Denmark).

Contact Details

For more information in relation to this news article, please contact:

Doctor Paul Gilson

Group Head, and Head of Burnet Cell Imaging Facility

Telephone

+61385062481

Email

paul.gilson@burnet.edu.au

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