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.
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).