The less-costly tobacco-plant derived vaccine will be targeted for the developing world.
The Zika virus, a flavivirus with devastating consequences for babies born of infected mothers, has garnered worldwide attention. Because of the dramatic and potentially deadly consequences of infection on unborn babies, researchers around the world have been scrambling to create an effective vaccine against the virus, particularly for areas where the infection is endemic, such as Brazil. Recently, researchers from Arizona State University (ASU) made great strides towards this goal, creating the world’s first plant-based Zika vaccine, which “could be more potent, safer, and cheaper to produce than any other efforts to date,” according to a press release on the research.
Led by ASU Biodesign Institute scientist Qiang “Shawn” Chen, PhD, the researchers from ASU utilized a key protein in the Zika virus, DIII, to develop this new vaccine. Dr. Chen elaborated on this protein in the press release, stating, “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.”
The team “first grew the envelope protein in bacteria, and then, switched to prepare the DIII protein domain in tobacco plants.” Immunization experiments were performed in mice after the team had developed enough material. These experiments elicited cellular and antibody immune responses in the mice which conferred 100% protection again multiple strains of the Zika virus in mouse challenge.
Of course, working in the confines of the laboratory without contributing factors will yield slightly different results than in the real world. Other vaccines that other researchers are developing around the world have also produced positive results in lab tests; however, prior exposure to other flaviviruses, as is many times the case in real-world settings, can have unwanted effects on vaccines that use the complete Zika envelope protein for their vaccine. Dr. Chen explained in the press release, “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. 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.”
These effects were shown in some animal experiments. Animals that had been previously exposed to dengue or West Nile virus had worse Zika infection and symptoms, which suggests a similar risk for individuals with prior exposure to dengue. (Such exposure would be common in areas, such as South America, where both viruses are endemic.) According to Dr. Chen, “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.”
This makes ASU’s protein-based vaccine that much more desirable in that it should be able to circumvent those interactions. The ASU vaccine uses “the smallest and most unique part of the Zika virus that can still elicit a potent and robust immune response.” Dr. Chen elaborated on this in the press release, stating, “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.” This makes Dr. Chen confident that the ASU vaccine is safer than other protein-based vaccines.
He continued, “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.”
Thanks to a grant from the National Institute of Allergy and Infectious Diseases (NIAID), seed funds from the Biodesign Institute, and federal, state, and public support, the team at ASU has been able to move from the idea for the vaccine to the proof-of-concept quickly. According to the press release, the team “hopes to partner with the medical community to begin the first phase of a human clinical trial in the next 2 years,” arguably welcome news for the hundreds of women who are faced with the threat of infection every day.
The full study was published online in Scientific Reports.