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ASU Biodesign scientists develop improved, potentially safer Zika vaccine

ASU takes a major step forward in boosting Zika prevention efforts.
August 9, 2017

Tobacco plant-produced vaccine could also be less costly, targeted for developing world

The worldwide Zika threat first emerged in 2015, infecting millions as it swept across the Americas. It struck great fear in pregnant women, as babies born with severe brain birth defects quickly overburdened hospitals and public health care systems.

In response, there has been a flurry of heroic scientific efforts to stop Zika.  Whole governments, academic labs and pharmaceutical companies have raced to develop Zika vaccines ever since global health experts first realized the dangers wrought by the mosquito-borne virus.

Now, Arizona State University has taken a major step forward in boosting Zika prevention efforts.

ASU Biodesign Institute scientist Qiang “Shawn” Chen has led his research team to develop the world’s first plant-based Zika vaccine that could be more potent, safer and cheaper to produce than any other efforts to date. 

“Our vaccine offers improved safety and potentially lowers the production costs more than any other current alternative, and with equivalent effectiveness,” said Chen, a researcher in the Biodesign Center for Immunotherapy, Vaccines and Virotherapy and professor in the School of Life Sciences. “We are very excited about these results.”

Rapid response network

Several potential Zika vaccines have had promising results in early animal and human tests. Last year, the Food and Drug Administration approved the first human testing of a Zika vaccine candidate, and this summer, a $100 million U.S. government-led clinical trial is underway.

But currently, there are no licensed vaccines or therapeutics available to combat Zika.

Several dedicated ASU scientists heeded the call to action, wanting to use their special know-how to find a way to overcome the pandemic crisis.

First, ASU chemist Alexander Green, along with collaborators at Harvard, developed a more rapid and reliable Zika test, an achievement highlighted by Popular Science in its “Best of What’s New” of 2016.

Now, Chen may have come up with a better vaccine candidate based on a key Zika protein. Chen is a viral expert who has worked for the past decade on plant-based therapeutics and vaccines against West Nile virus and dengue fever, which come from the same Zika family, called flaviviruses.

He honed in on developing a vaccine against a part of a Zika viral protein, called DIII, that plays a key role for the virus to infect people. 

“All flaviviruses have the envelope protein on the outside part of the virus. It has three domains. The domain III has a unique stretch of DNA for the Zika virus, and we exploited this to generate a robust and protective immune response that is unique for Zika,” Chen said.  

They first grew the envelope protein in bacteria, then switched to prepare the DIII protein domain in tobacco plants.

After developing enough material for the new vaccine candidate, Chen’s team performed immunization experiments in mice, which induced antibody and cellular immune responses that have been shown to confer 100 percent protection against multiple Zika virus strains in a mouse challenge.

Producing plant-based vaccines, especially in tobacco plants, is old hat for ASU researchers like Chen. For more than a decade, they’ve been producing low-cost vaccines in plants to fight devastating infectious diseases in the developing world.

It’s the same approach ASU plant research pioneer Charles Arntzen used when he played a key role in developing ZMapp, the experimental treatment used during the Ebola outbreak.

Artntzen’s Biodesign colleagues, including Chen, Hugh Mason and Tsafrir Mor, have continued to pursue plant-based vaccines and therapeutics to combat West Nile virus, dengue fever, nerve agents and even cancer.

Effective but not foolproof

While Chen has been cheering on Zika vaccine progress from other researchers, in each case there can be side effects.

To date, other scientists have tested several kinds of vaccines on mice — including one made from DNA and another from an inactivated form of the virus. With just one dose, both vaccines prompted the creation of antibodies that shielded the animals from becoming infected when they were exposed to the virus.

Any heat-killed vaccine runs the risk of accidentally injecting a live version of the virus if there is an error made in the vaccine production protocol. This tragic scenario happened occasionally with the polio vaccine.

For the second research group, they used the complete Zika envelope protein for their vaccine. Since envelope protein domains I and II are similar to West Nile and dengue viruses, this can cause a dangerous cross-reactive immune response.

“When you make the full native envelope protein as the basis for a vaccine, it will induce antibodies against DI, DII and the DIII domains of the protein,” Chen explained. “Those who have been prior exposed to DI and DII of other members of the Zika virus family may be prone to developing very bad symptoms, or in some cases, fatalities for dengue.”

In fact, animal experiments have shown that prior exposure to dengue or West Nile virus makes the Zika infection and symptoms much worse, suggesting a similar risk for people who had prior exposure to dengue (especially in South America, where it is more common).

“If you have prior exposure to dengue, and then have Zika exposure, the Zika infection may be much worse, and for men, may increase the likelihood of sexual transmission,” Chen said.

Chen’s protein-based vaccine uses the smallest and most unique part of the Zika virus that can still elicit a potent and robust immune response.

“In our approach, we make what we call a pseudovirus. It’s a fake virus. The pseudovirus displays only the DIII part of the envelope protein on the surface. This is at least as potent as previous vaccine versions.”

And he is very confident that his DIII-based protein vaccine will be safer.

“We did a test to make sure that the vaccine produces a potent protective immune response, but also, that it does not produce antibodies that may be cross-reactive for dengue, West Nile, yellow fever or others,” Chen said.

Fast track to the clinic

During the height of the Zika pandemic, whole countries of women were told not to become pregnant, due to babies born with a severe brain defect called microcephaly, in which the head and brain don't develop properly.

There have also been vision and hearing defects and learning disabilities associated with less severe infections.

To make matters worse, in adults, a debilitating nervous system condition called Guillain-Barre syndrome has also been shown to be caused by Zika.

While the most severe wave of the Zika pandemic has ebbed, it won’t go away anytime soon, and a vaccine still offers the best hope.

Tens of millions more could still be infected in the Americas in the coming years (see WHO fact sheet).

The ASU scientists were able to mobilize quickly from idea to proof-of-concept because they could leverage funds from an NIAID grant and seed funds from the Biodesign Institute.  

These are all made possible by generous federal, state and public support, including sales tax generated from the longtime Arizona innovation booster, voter-approved Proposition 301.

“This is a great example of the brightest minds quickly coming together, with public support, to take on one of the most significant public health challenges of our time,” said Josh LaBaer, executive director of the Biodesign Institute.

“That’s the essence of Biodesign at its best, and we hope this important proof-of-principal of a Zika vaccine can be translated quickly into the clinic.”

With the successful proof-of-principle, Chen hopes to partner with the medical community to begin the first phase of a human clinical trial in the next two years.

“Above all, we have to ensure the utmost safety with any Zika vaccine, especially because the people who will need it most, pregnant women, have the most worries about their own health, and the health of the fetus,” Chen said. “This has to be 100 percent safe and effective.”

Along with Chen, the research team included Ming Yang, Huafang “Lily” Lai and Haiyan Sun.

The research was published in the online version of Scientific Reports - Nature.

 

Top photo: ASU Biodesign Institute scientist Qiang “Shawn” Chen has led his research team to develop the world’s first plant-based Zika vaccine that could be more potent, safer and cheaper to produce than any other efforts to date.  

Joe Caspermeyer

Managing editor , Biodesign Institute

480-258-8972

 
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ASU Regents' Professor and diamond expert examines scientific uses for gemstone.
August 10, 2017

ASU professor exploring ways to use diamonds in electronics, cancer, space

Diamonds are among the most coveted objects in the world. As gemstones, they are brilliant, rare and symbolic. As a raw material, they are a physicist’s best friend.

If you think about certain characteristics of a material — hardness, for example, or ability to conduct heat — diamonds are usually at one extreme end of the spectrum.

“It’s surprising that a material so simple, just carbon atoms arranged in this cubic crystal system, has such unusual properties in so many ways,” said Robert Nemanich, a Regents’ Professor of physicsThe Department of Physics is a unit of the College of Liberal Arts and Sciences. at Arizona State University.

As one of the world’s foremost experts on diamonds, Nemanich knows what they are capable of. And he has a different sort of proposal for how to use them.

Doping diamonds for better electronics

Diamonds are the overachievers of the materials world. They can sustain incredibly high temperatures and electric fields. They also conduct heat better than any other material. These properties make them ideal for very specific applications.

Currently, silicon dominates the electronics market. It’s used to make everything from your cellphone computer chip and laptop processor to microwave ovens. But as versatile as silicon is, there are certain areas where it falls flat.

“When it comes to high-temperature, high-power, radiation-hard devices, silicon doesn’t work as well. In fact, it doesn’t work at all,” said Manpuneet Kaur Benipal, a postdoctoral researcher in Nemanich’s lab.

Benipal and her colleague Brianna Eller both received their doctorates from ASU. With Nemanich as an adviser, they are now starting a company, ADVENT Diamond, to make electronic devices out of diamond.

But we’re not talking about using recycled wedding rings. Eller and Benipal are working with doped diamond layers grown on small diamond plates. The ASU team even has a patent in the works for part of the growth process, called doping.

Take a tour of Robert Nemanich's lab and learn more about doping diamonds.

The term “doping” may conjure images of athletes illegally growing their muscles, but in the materials field, doping allows scientists to grow diamonds specifically for electronic purposes. Here’s how it works: You take a diamond substrate, or a small sample of diamond, and immerse it in a plasma composed of a mixture of chemicals. The atoms from the added chemicals organize themselves on the surface of the diamond, replicating the crystal structure of the substrate.

The lab-grown diamond layers that result include impurities that change the material’s electrical properties. Benipal and Eller use microfabrication processing of the doped diamond layers so that they behave precisely in the way they want. The process works so well that a small diamond can do the same work as materials that are much larger in size.

Does this mean we can expect to see tiny diamonds in our smartphones soon? Not exactly. Silicon continues to be more cost-effective for low-temperature applications, like cellphones and laptops. But diamond is a good choice for anything with a high-powered engine, such as an electric vehicle or an aircraft. Because diamond is excellent at conducting away heat, it would completely replace the need for a cooling system. Diamond also works well at very high pressures, which makes it perfect for deep-earth drilling.

More precise cancer treatment

We know diamonds’ ability to withstand extreme heat and pressure makes them superheroes in the world of electronic devices. But they have another power that scientists are harnessing to improve an entirely different field — cancer treatment.

Diamond is radiation-hard, meaning it takes much longer than most other materials to degrade under X-rays, gamma rays and fast charged particles. This property makes diamonds an ideal material to build radiation detectors for a variety of applications, including proton beam technology. This is a form of radiation therapy that precisely targets and destroys tumors with highly charged subatomic particles called protons.

Researchers at Nemanich’s lab, along with proton beam experts at Mayo Clinic Arizona, are working together to see if the use of diamond detectors can further enhance proton beam’s benefits to patients. Mayo Clinic is currently the only site in the Southwest to offer the technology.

Mayo Clinic’s intensity-modulated proton beam therapy features pencil beam scanning, which deposits streams of protons back and forth through a tumor. The beam closely targets the tumor, while largely sparing surrounding healthy tissue and organs from its radiation.

The researchers are studying to see if diamonds can be used as a detector for the pencil beam to go through. This could possibly help radiation oncologists further fine-tune the path of the protons, which could be particularly beneficial for pediatric patients.

“It’s most important in children to spare healthy tissues because those tissues are still growing, so we have to be very careful to treat as little of the healthy tissue as possible,” said Martin Bues, a proton beam physicist and researcher at Mayo Clinic’s Phoenix campus who is working with Nemanich and the ASU team on this project.

man in lab
“It’s surprising that a material so simple, just carbon atoms arranged in this cubic crystal system, has such unusual properties in so many ways,” said Robert Nemanich, a Regents’ Professor of physics at Arizona State University. Photo by Charlie Leight/ASU Now

A diamond in the sky

If diamond is a material superhero, perhaps it’s only fitting that scientists want to send it into space. Nemanich was recently awarded a grant from NASA to build diamond electronics for a rover that will explore the surface of Venus.

“Venus is 450 degrees centigrade,” Nemanich said, “So it’s very, very hot.”

How hot, exactly? To give you an idea, 450 degrees centigrade is about 842 degrees Fahrenheit. In comparison, the hottest weather ever recorded on Earth was a mere 129 degrees F, in Death Valley, California, in 2013.

Through the NASA grant, Nemanich and his team are building an amplifier, a device that increases the power of an electrical signal. But Eller said that diamond could be useful for other parts of the rover as well, since very few other materials can function in such extreme heat.

As demand for high-powered electronics increases, diamonds will have an even larger role to play. Space exploration, electronic vehicles and deep-earth drilling only scratch the surface of potential applications.

Just as silicon brought about a new era of electronics, novel materials often drive the progress of new systems and devices. Perhaps the most exciting applications for diamonds are those that haven’t been thought of yet, since diamond would enable them to be built.

“There is always a need for something bigger, something better, something more efficient, something that works at higher temperature or higher voltage, which we think diamond can do,” Eller said.

Allie Nicodemo

Communications specialist , Office of Knowledge Enterprise Development

480-727-5616