In early 2016, the World Health Organization declared the Zika virus an international public health emergency as the mosquito-transmitted disease began spreading from its epicenter in Brazil to the United States and other countries in the Western Hemisphere. In the three years since its emergence in 2015, there have been more than 223,000 confirmed cases of the Zika virus worldwide, with infected women giving birth to more than 3,700 babies with brain abnormalities and other serious problems.
As public concern grew, physicians and scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, were already hard at work developing a vaccine for this devastating disease.
Led by Dr. Barney Graham, deputy director of the Vaccine Research Center, and Ted Pierson, chief of the Laboratory of Viral Diseases, the NIH researchers created a promising vaccine for the Zika virus in 2016 with lightning speed.
The vaccine moved from inception to manufacturing in just three months, an exceptionally short timeframe. A Phase 1 clinical trial to test for safety began three months later, and the vaccine moved to a Phase 2 clinical trial in March 2017 to measure its effectiveness. If successful, the vaccine will be tested in a larger Phase 3 clinical trial, and if it proves to be effective, the next step will be review by the Food and Drug Administration.
“The speed of designing and developing a vaccine and getting into human trials was really unprecedented,” said Dr. John Mascola, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases. “Barney Graham and Ted Pierson realized that there was an epidemic going on and that the more rapidly that they could bring a vaccine forward, the more likely it could have an effect.”
Both men were well-suited for the task. Graham is an immunologist, virologist and clinical trials physician with a specialty in vaccine development. Pierson is an expert on viruses transmitted by infected ticks or mosquitos, such as West Nile virus, dengue virus and tick-borne encephalitis.
One challenge the NIH team now faces is that the Phase 2 clinical trial is occurring during a period without a severe Zika outbreak, so there is less data available about infected populations. But Dr. Steven Holland of the National Institute of Allergy and Infectious Diseases said the team is persisting because the need for the vaccine remains critical. In addition to the NIH effort, a Japanese pharmaceutical company is testing a different Zika vaccine that is in the early stages of development.
“We know Zika is going to reemerge, but we don’t know when,” Holland said. “And if we are not ready, we will go through exactly the same sort of absolutely tragic loss of time and effort in the future. This is our chance to get it right for children and adults down the road.”
One recent study projected that a pregnant woman who becomes ill from the Zika virus faces a 7 percent chance that her child will be born with birth defects. That risk jumps to nearly 13 percent if the women becomes ill during the first trimester.
In 2015, before the Zika virus became national news, Graham was informed by a Brazilian doctor at a medical conference about a growing number of babies born with abnormally small heads and underdeveloped and damaged brains.
“Even though it wasn’t confirmed and it sounded sort of like tabloid news, we decided that we should at least be prepared to start a Zika vaccine program,” Graham said.
By the time Zika was declared a global public health crisis, Graham and Pierson had started examining hundreds of vaccine design ideas and were using new DNA technology that enabled the vaccine they developed to mimic the Zika virus and trigger the body to mount an immune response.
Graham and Pierson developed new testing methods, and accelerated the process by doing in vitro and in vivo testing concurrently. In rapid succession, they created both a lead and backup vaccine candidate distinguished by their genetic and physical structures. The team conducted animal studies to determine effectiveness, and concurrent Phase I human trials to demonstrate safety, quickly concluding the backup was a better candidate for advanced human testing.
“If and when the Zika virus vaccine is approved for public use, there is no question it will have a tremendous impact on the lives of families,” Holland said. “Graham and Pierson and their teams provide a model for how to respond quickly to an emerging pathogen and a blueprint for better preparedness for future pandemics.”