Malaria is a mosquito-borne disease caused by infection with protozoan parasites from the genus Plasmodium. It affects more than 225 million people worldwide in tropical and subtropical regions, resulting in fever, headaches and in severe cases coma and death. While a variety of often costly antimalarial medications are available to travelers in those regions to protect against infections, a vaccine offering a high level of protection from the disease does not yet exist.
The use of algae to produce malaria proteins that elicited antibodies against Plasmodium falciparum in laboratory mice and prevented malaria transmission was published today in the online, open-access journal PLoS ONE. The development resulted from an unusual interdisciplinary collaboration between two groups of biologists at UC San Diego—one from the Division of Biological Sciences and San Diego Center for Algae Biotechnology, which had been engineering algae to produce bio-products and biofuels, and another from the Center for Tropical Medicine and Emerging Infectious Diseases in the School of Medicine that is working to develop ways to diagnose, prevent and treat malaria.
Part of the difficulty in creating a vaccine against malaria is that it requires a system that can produce complex, three-dimensional proteins that resemble those made by the parasite, thus eliciting antibodies that disrupt malaria transmission. Most vaccines created by engineered bacteria are relatively simple proteins that stimulate the body’s immune system to produce antibodies against bacterial invaders. More complex proteins can be produced, but this requires an expensive process using mammalian cell cultures, and the proteins those cells produce are coated with sugars due to a chemical process called glycosylation.
“Malaria is caused by a parasite that makes complex proteins, but for whatever reason this parasite doesn’t put sugars on those proteins,” said Stephen Mayfield, a professor of biology at UC San Diego who headed the research effort. “If you have a protein covered with sugars and you inject it into somebody as a vaccine, the tendency is to make antibodies against the sugars, not the amino acid backbone of the protein from the invading organism you want to inhibit. Researchers have made vaccines without these sugars in bacteria and then tried to refold them into the correct three-dimensional configuration, but that’s an expensive proposition and it doesn’t work very well.”
Instead, the biologists looked to produce their proteins with the help of an edible green alga, Chlamydomonas reinhardtii, used widely in research laboratories as a genetic model organism, much like the fruit fly Drosophila and the bacterium E. coli. Two years ago, a UC San Diego team of biologists headed by Mayfield, who is also the director of the San Diego Center for Algae Biotechnology, a research consortium seeking to develop transportation fuels from algae, published a landmark study demonstrating that many complex human therapeutic proteins, such as monoclonal antibodies and growth hormones, could be produced by Chlamydomonas.
That got James Gregory, a postdoctoral researcher in Mayfield’s laboratory, wondering if a complex protein to protect against the malarial parasite could also be produced by Chlamydomonas. Two billion people live in regions where malaria is present, making the delivery of a malarial vaccine a costly and logistically difficult proposition, especially when that vaccine is expensive to produce. So the UC San Diego biologists set out to determine if this alga, an organism that can produce complex proteins very cheaply, could produce malaria proteins that would inhibit infections from malaria.
“It’s too costly to vaccinate two billion people using current technologies,” explained Mayfield. “Realistically, the only way a malaria vaccine will ever be used is if it can be produced at a fraction of the cost of current vaccines. Algae have this potential because you can grow algae any place on the planet in ponds or even in bathtubs.”
Collaborating with Joseph Vinetz, a professor of medicine at UC San Diego and a leading expert in tropical diseases who has been working on developing vaccines against malaria, the researchers showed that the proteins produced by the algae, when injected into laboratory mice, made antibodies that blocked malaria transmission from mosquitoes.
“It’s hard to say if these proteins are perfect, but the antibodies to our algae-produced protein recognize the native proteins in malaria and, inside the mosquito, block the development of the malaria parasite so that the mosquito can’t transmit the disease,” said Gregory.
“This paper tells us two things: The proteins that we made here are viable vaccine candidates and that we at least have the opportunity to produce enough of this vaccine that we can think about inoculating two billion people,” said Mayfield. “In no other system could you even begin to think about that.”
The scientists, who filed a patent application on their discovery, said the next steps are to see if these algae proteins work to protect humans from malaria and then to determine if they can modifiy the proteins to elicit the same antibody response when the algae are eaten rather than injected.
Other UC San Diego scientists involved in the discovery were Fengwu Li from Vinetz’s laboratory and biologists Lauren Tomosada, Chesa Cox and Aaron Topol from Mayfield’s group. The basic technology that led to the development was supported by the Skaggs family. The research was supported by grants from the National Institute of Allergy and Infectious Diseases and the San Diego Foundation. The California Energy Commission supported work on recombinant protein production for biofuels use, and this technology helped enabled these studies.
The PLoS ONE article can be accessed at: http://dx.plos.org/10.1371/journal.pone.0037179
UC San Diego News on the web at: http://ucsdnews.ucsd.edu
Kim McDonald | Newswise Science News
Further reports about: > Algae > Biologists > Biotechnology > Chlamydomonas > Chlamydomonas reinhardtii > Infectious Diseases > Medicine > PLoS One > Plasmodium falciparum > Vaccine > infectious outbreaks > laboratory mice > malaria proteins > malaria transmission > mosquito-borne disease > protozoan parasite > subtropical region > tropical disease
New gene potentially involved in metastasis identified
26.03.2019 | Institute of Science and Technology Austria
Decoding the genomes of duckweeds: low mutation rates contribute to low genetic diversity
26.03.2019 | Westfälische Wilhelms-Universität Münster
Cancers that display a specific combination of sugars, called T-antigen, are more likely to spread through the body and kill a patient. However, what regulates...
DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.
The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...
Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.
The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...
Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.
Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...
The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.
A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...
11.03.2019 | Event News
01.03.2019 | Event News
28.02.2019 | Event News
26.03.2019 | Physics and Astronomy
26.03.2019 | Physics and Astronomy
26.03.2019 | Physics and Astronomy