PHILADELPHIA -- A new generation DNA-based Zika vaccine is the first to demonstrate both safety and the ability to elicit an immune response against Zika in humans, according to new research from the Perelman School of Medicine at the University of Pennsylvania, conducted in partnership with The Wistar Institute, Inovio Pharmaceuticals, and GeneOne Life Science, Inc. In results published today in the New England Journal of Medicine, the phase 1 clinical trial showed for the first time that humans who received up to three doses of the vaccine candidate produced an immune response against Zika with minimal adverse effects, opening the door to further clinical trials for this important vaccine candidate.
The GLS-5700 vaccine is a synthetic DNA vaccine that contains the instructions for the host to mount an immune response against a specific Zika virus antigen.
"Zika virus continues to be a threat to people living in the Americas and the Caribbean," said the study's lead author, Pablo Tebas, MD, a professor of Infectious Diseases at Penn. "With these new results, we are one step closer to hopefully finding a way to prevent infection, which can cause serious birth defects and developmental delays in babies born to women who are infected with Zika."
In 2015 and 2016, Zika virus spread rapidly through Brazil, the Caribbean, and even into the southern United States. However, a vaccine to prevent infection has remained elusive.
Researchers in Philadelphia, along with research teams from Miami and Quebec City enrolled 40 participants in the safety trial between August and September of 2016. Two groups of 20 participants received either one or two milligram doses of the vaccine candidate intradermally at zero, four, and 12 weeks. Each dosage was followed by the delivery of small electric currents into the skin at the site of injection, known as electroporation (EP), to facilitate optimal vaccine uptake, production of the intended antigen, and immune responses.
Two weeks after participants received the third and final dose of the vaccine, 100 percent developed Zika-specific antibodies and 80 percent developed significant neutralizing antibodies against the virus. Importantly, serum from the study participants was able to protect immune-compromised mice from developing the disease after infection with Zika virus, indicating that the vaccine-induced antibodies can prevent infection and disease in vivo. No serious adverse effects were reported. Minor adverse effects included injection site pain, redness, and swelling.
"Synthetic DNA vaccines, such as this Zika vaccine candidate our team has developed, are an important approach to preventing emerging infectious diseases," said David Weiner, PhD, executive vice president of The Wistar Institute, director of Wistar's Vaccine & Immunotherapy Center, and co-lead author of the study. "This novel DNA vaccine was developed and implemented in just months via a platform that has advantages in temperature stability, storage, dose, and distribution compared to most traditional vaccines, making DNA vaccines an important tool to respond quickly to curb an emerging epidemic."
Further study is required to fully address the efficacy of this Zika vaccine candidate; however, this study suggests that a DNA vaccine can produce antibodies associated with Zika protection as well as T-cells in a well-tolerated platform, which can be rapidly implemented to target infectious disease.
"Our results show great promise that synthetic DNA vaccines for Zika and other viruses, such as Chikungunya, West Nile Virus, Pandemic Influenza or Ebola, are likely important as viable options for the future of vaccines," Tebas said.
Joel Maslow, MD, chief medical officer of GeneOne Life Science Inc. was also a lead author on this study.
Funding for the research was provided in part by the National Institutes of Health (AI069534) and by GeneOne Life Science, Inc.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.
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Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.