Now Hugo Luján, a Howard Hughes Medical Institute international research scholar, reports that Giardia's extensive wardrobe of surface proteins might actually be its own downfall.
In an advance online publication in the journal Nature Medicine on April 25, 2010, Luján shows that Giardia parasites engineered to express all their surface proteins worked as vaccines that could help prevent or mitigate future infections. The same "overdressed" parasites offer protection when given orally to gerbils infected with Giardia, he says, though the idea still needs to be tested in humans.
Luján believes Giardia's hardy surface proteins—which help the parasite thrive in the harsh, acidic environments of the stomach and upper intestine—might eventually be used to deliver vaccines not just against Giardia but other parasites too, including malaria. "They could allow us to save money and lives," he says. "These proteins help the parasite survive but we're planning to use that armor to make new, oral vaccines."
A professor at the Catholic University of Córdoba, in Argentina, Luján's fascination with Giardia dates back to his days as a postdoctoral fellow in parasitology, working with Theodore Nash at the National Institutes of Health. Luján remembers being intrigued by Giardia's simplicity. Confining the parasite to a culture tube had no effect on its lifecycle, which made it easy to study and manipulate the organism. Upon returning to Argentina, Luján continued his research on Giardia, and in 2008, he reported that the shifty organism changes its appearance between 200 different protein coats using a molecular process called RNA interference (RNAi). As proof that RNAi was critical to the bug's "invisibility," he disabled its RNAi mechanism, and found that all the surface proteins appeared at once.
Luján reasoned that this genetically-altered parasite might make an optimal vaccine. Ordinarily, children in developing countries suffer the most from routine Giardia infections, which they usually get from drinking contaminated water. Adults rarely get as sick because they have built up immunity from earlier contact with the parasite. Luján's hypothesis was that a child exposed to all Giardia's surface proteins at once would be primed to resist any future infection.
Luján's team tested out the hypothesis on gerbils, which are a good model for scientists because they can be infected with the same Giardia parasites that attack humans. Those exposed to parasites expressing just one surface protein were re-infected easily by parasites expressing a different surface protein. But gerbils that had been exposed to a strain of Giardia that expressed all 200 surface proteins were less likely to be reinfected. Another welcome surprise was that the isolated proteins were non-toxic and elicited an immune response. According to Luján, this is the first time researchers have generated a vaccine purely from proteins, which can be stored at room temperature and delivered orally, both necessities for a vaccine that can be easily delivered in the developing world.
Luján plans to leverage the proteins' resistance to gastrointestinal enzymes by testing whether they can ferry other oral vaccinations into the body. In many cases, the surface proteins expressed by infectious pathogens are destroyed in the gastrointestinal tract before the immune system has a chance to respond. That's in part why oral vaccines for illnesses like malaria haven't been practical. But if attached to surface proteins from Giardia, Luján says, these antigens might survive in the gastrointestinal tract long enough to be recognized by the immune system.
"This could be a huge development," says Luján, who recently filed a patent application on his research with the U.S. Patent and Trademark Office. "Hopefully, we'll be able to use this system to make vaccinations that we can give in a very convenient way. Giardia's surface proteins are fascinating, and now we're finding that we can exploit what the parasite uses to defend itself to our own favor."
Andrea Widener | EurekAlert!
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Materials Sciences
19.10.2017 | Materials Sciences
19.10.2017 | Physics and Astronomy