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DNA-based Zika vaccine development continues after promising early data
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PHILADELPHIA – The Wistar Institute recently hosted a Q&A discussion panel event during which researchers shared promising new developments for a DNA-based vaccine as a preventive measure against the mosquito-borne Zika virus.
The panel — titled “Zika: What You Need to Know” — comprised four experts from The Wistar Institute and Inovio Pharmaceuticals Inc. The moderator was Paul A. Offit, MD, director of the Vaccine Education Center and professor of pediatrics in the division of infectious diseases at The Children’s Hospital of Philadelphia. The panelists included David B. Weiner, PhD, executive vice president of The Wistar Institute, director of The Wistar Institute Vaccine Center, and the W.W. Smith Charitable Trust Professor in Cancer Research; Gary Kobinger, PhD, professor in the department of microbiology and infectious diseases and director of the research center on infectious diseases, faculty of medicine at Universite Laval; Niranjan Y. Sardesai, PhD, COO of Inovio Pharmaceuticals Inc.; and Pablo Tebas, MD, professor of medicine at the Hospital of the University of Pennsylvania.
“There are many obstacles in developing a vaccine for Zika, because though it’s been around since 1947, the horrific birth and brain defects including microcephaly were really not apparent until this year,” Weiner told Infectious Diseases in Children prior to the panel discussion. “There were no agents, there were no models, no pathway, no agreement on what may protect or not protect. So, in this case of vaccine development, everything had to be developed on the fly, so to speak.”
The Wistar Institute Vaccine Center and GeneOne Life Science Inc. collaborated on a preclinical study published in npj Vaccines that involved animal models, including mice, randomly assigned into experimental and control groups. The experimental groups were vaccinated with the synthetic DNA Zika vaccine, followed by exposure to the Zika virus. Among vaccinated animal models, 100% demonstrated immunity to the virus exposure challenge. In addition, vaccination yielded protection to the antigen-specific antibody prME and neuroprotection, halting the disease from spreading to the brain and causing damage.
“During vaccine development, asymptomatic people are vaccinated to develop an immune response that will protect them from infection from the pathogen so the body is prepared to fight the pathogen,” Sardesai told Infectious Diseases in Children in an interview. “For the DNA-based vaccine development, we are taking a single antigen of the virus; the rest of the virus is not there. We use the single antigen in the vaccine, and the body produces the antigen and produces an immune response against it.”
According to the CDC, there have been 4,000 cases of Zika infection reported in the U.S. Most cases are related to travel to areas where the virus is emerging; however, more than 100 cases originating in the U.S. have been reported as well. It is important, then, for the researchers to examine the effects of vaccination in infected persons to gather data regarding in whom the virus incurs illness.
The vaccine would be administered to travelers presently if it were FDA-approved soon because the Zika virus does not circulate concurrently, Offit said during the panel discussion. “My understanding is that 80% of Zika virus infections are asymptomatic and 20% are symptomatic, and most symptomatic infections occur in people who have traveled to an area where the epidemic is prevalent.”
David B. Weiner
“Inactivated viral vaccines have complexities and side-effects associated with Zika,” Tebas said during the panel discussion. “Infected individuals could experience side effects and consequently be infected with dengue [in developing countries].”
The Zika vaccine development is shared between The Wistar Institute, GeneOne Life Science Inc. and Inovio Pharmaceuticals and is presently undergoing testing for safety and efficacy in two human phase 1 clinical trials approved by the FDA. Inovio expects to report data from the 40-person trial conducted in Miami, Philadelphia and Quebec City prior to the end of 2016. Results from the study including 160 participants in Puerto Rico are expected to be available by mid-2017.
“This vaccine is our best hope for Zika and microcephaly because mosquito control has not worked in controlling dengue; it still has an impact on that area,” Kobinger said in an interview. “Even with Zika being a flavivirus, there is still not enough known about the virus. We have never seen animal testes atrophy unilaterally or bilaterally in response to any other flavivirus like we have seen exhibited with Zika, and what is known about West Nile, yellow fever, dengue is not always applicable to Zika.”
A successful Zika vaccine will have a huge impact on the epidemic; travelers could be vaccinated before going to an affected area and not worry about viral infection, and people living in endemic areas could develop immunity prior to exposure, Weiner said. – by Kate Sherrer
Disclosure: Sardesai is COO of Inovio Pharmaceuticals Inc. Weiner received funding from Inovio Pharmaceuticals Inc. and Gene One Life Science Inc. All other panel members report no relevant financial disclosures.