Parasite Helps in Malaria Fight

Malaria afflicts hundreds of millions of people every year, killing hundreds of thousands. The effort to make a vaccine against malaria has been ongoing for more than a century. Senior Research Scientist José A. Fernández Robledo is working to bring an unlikely ally into the fray: an oyster parasite.

Perkinsus marinus, a parasite innocuous to humans, has caused widespread oyster mortalities along the East Coast and beyond. However, Fernández Robledo is utilizing genetic engineering techniques to harness this deadly organism for good.

In 2016, a student in his laboratory showed that Perkinsus can express genes of Plasmodium, the parasite that causes malaria. Fernández Robledo’s team also showed that Perkinsus cells engage the immune system in mammals, suggesting that they could deliver a vaccine to humans. This work was performed in collaboration with the U.S. Military Malaria Vaccine Program, the Naval Medical Research Center, and the Walter Reed Army Institute of Research.

“Plasmodium has always foiled attempts to develop efficient malaria vaccines in the past,” Fernández Robledo said. “This oyster parasite offers an opportunity for us to put genomes to work to solve an ongoing public health problem.”

He hopes that genetically engineering Perkinsus will create a new platform for vaccine delivery, which could one day have global importance for public health. For now, he must think infinitesimally smaller: at the scale of individual genes.

First, Fernández Robledo will select Plasmodium genes that seem like promising candidates for the vaccine. He will use molecular techniques to insert a trial gene into Perkinsus cells in the lab and test whether the gene is ultimately integrated into the organism’s genome. Successful integration will be a significant step in producing antigenic proteins that can act as vaccines against malaria.

“This shows the potential of placing marine microorganisms outside of their ecological niches under laboratory conditions,” Fernández Robledo said.

Recent technological advances make the time ripe for such innovation. This project will make use of CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats), a tool that allows scientists to edit genomes with high precision.

“New genetic techniques, like CRISPR/Cas9, dramatically simplify and speed up this work,” Fernández Robledo said. “They are revolutionizing science and the ability to quickly explore hidden potential in almost any genome.”

The malaria vaccine project, a collaboration with the University of Maine and Southern Maine Community College, will also serve as a training ground for the next generation of synthetic biologists. A master’s student from the University of Maine will work to optimize the growth of the parasite in bioreactors, allowing the team to work on an industrial scale and have greater control over their parasite culture. Two Southern Maine Community College students will spend two months at Bigelow Laboratory during the summers of 2019 and 2020, working with students in the Research Experience for Undergraduates program.

Utilizing education and cutting-edge techniques will likely prove key to tackling the malaria vaccine problem that has stymied scientists for so long. Fernández Robledo says the method he is developing can be applied to any other infectious disease, from Zika virus to the common flu.

“This is a unique approach we can explore as marine scientists,” Fernández Robledo said. “Medical doctors aren’t likely to look to an oyster parasite when trying to develop a vaccine against human pathogens.”