USF plays role in study showing DNA-based Zika vaccine protects against infection, brain damage

USF Health Morsani College of Medicine immunologist Kenneth Ugen, PhD, participated in a new study demonstrating how a synthetic DNA vaccine approach successfully protected against infection, brain damage and death caused by the mosquito-borne Zika virus in vivo.

Dr. Ugen, a professor in the Department of Molecular Medicine, was a co-investigator for the preclinical study, recently published in the journal Nature: npj Vaccines. David B. Weiner, PhD, executive vice president and director of the Vaccine Center at The Wistar Institute in Philadelphia, was the study’s lead author.

“The paper published presents a study demonstrating the ability of a gene-based vaccine against a Zika virus protein to successfully protect mice from infection with this virus and associated damage,” Dr. Ugen said.

In this multisite study, 100 percent of the animal models were protected from Zika after vaccination followed by a challenge with the Zika virus. In addition, they were protected from degeneration in the cerebral cortex and hippocampal areas of the brain, while the other cohort showed degeneration of the brain after Zika infection.

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A microscopic image of the Zika virus.

The research was the first of its kind to analyze a vaccine in an animal model that is susceptible to the disease, providing information regarding the protective impact of the immune response in susceptible individuals. Prior studies of the Zika virus have tested vaccines in animal models that are naturally resistant to Zika. This study extends these prior research studies in an important manner.

In this latest study, Weiner and colleagues demonstrated how a synthetic DNA vaccine expressed specific antigens for Zika in vivo. They observed that this novel vaccine generated robust antigen-specific antibody and T cell responses that neutralized the virus in preclinical animal models. Moreover, they found that the vaccine provided protection against the disease and death in animal models while also being neuroprotective, meaning that the disease was unable to spread to the brain. This is especially important given the risk that infants born with the disease have of developing microcephaly, a birth defect resulting in an abnormally small head and that may prevent the brain from developing properly.

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Ken Ugen, PhD

One important aspect of Zika and many other mosquito-borne diseases is that not everyone infected with the virus will actually become ill as a result. With Zika, only about 20 to 25 percent of individuals with the virus are actually impacted by the disease, according to previous studies from the U.S. Centers for Disease Control (CDC). However, there is no way to know for certain who will be at risk for illness due to the virus, which is why it was crucial for this study to examine how a vaccine would operate in an infected, symptomatic host.

This Zika vaccine was developed by investigators at the Wistar Institute and Inovio Pharmaceuticals, with contributions from other investigators at multiple institutions. The vaccine has been approved by the FDA for clinical evaluation in Phase I clinical trials now being conducted in several U.S. and Canadian cities as well as in Puerto Rico.

Nearly 4,000 cases of Zika infection have been reported in the United States alone, according to the CDC. While most of these are travel-associated cases, more than 100 cases of Zika infection originating within the United States have been reported. Globally, more than 60 countries have reported mosquito-borne transmission of the disease.

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This work was supported by the National Institutes of Health and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases grant NIH R01 AI092843. Weiner received funding from Inovio Pharmaceuticals Inc. and Gene One Life Science Inc.