A clinical trial to evaluate a candidate vaccine for Zika virus is underway, with preliminary results from the multisite phase I trial expected by the end of 2016.
Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, announced the trial and gave an update about other Zika virus vaccine development efforts during an Aug. 3 telephone briefing with reporters. The announcement came just days after the continental United States saw its first cases of local transmission of Zika virus in Florida.
The phase I clinical trial began on Aug. 2 and will evaluate the safety and immunogenicity of an investigational DNA vaccine for Zika virus. This vaccine is similar to one that early-stage trials have shown to be safe and immunogenic for West Nile virus, a flavivirus closely related to Zika. The Zika virus vaccine had promising preclinical results, Dr. Fauci said. “Preliminary immune responses that we’ve seen in a variety of animal models have been rather robust.”
The DNA vaccine uses a plasmid to deliver genes that code for specific Zika virus proteins. “When the plasmid expresses the envelope protein from the Zika virus, it does so in a way that mimics the virus,” provoking a host immune response that includes neutralizing antibodies and T cells, according to lead trial investigator Julie Ledgerwood, DO, chief of the clinical trials program at the NIAID’s Vaccine Research Center.
The phase I clinical trial will enroll 80 healthy volunteers, aged 18-35 years. All participants will receive the investigational Zika virus vaccine at their first visit, with vaccine delivery via a needle-free system that injects the vaccine directly into the deltoid muscle.
Forty participants will receive one additional dose of the vaccine, with half of those people receiving the additional dose at 8 weeks after the first vaccine, and the other half receiving the additional dose at 12 weeks after the first dose. The other 40 participants will receive two additional doses, with half receiving them at 4 and 8 weeks after the first vaccination, and the other half receiving the extra doses at 4 and 20 weeks. All participants will receive the same dose at each vaccination.
Participants will be asked to monitor their temperature daily for a week after each vaccine dose is received; they will also report any adverse events. The trial design provides for several follow-up visits to track safety and to measure immune response in 44 weeks of short-term follow-up. Additionally, two follow-up visits at 18 months and 2 years post vaccination will measure the durability of the immune response.
The clinical trial will be run at the National Institutes of Health Clinical Center in Bethesda, Md., at Emory University in Atlanta, and at the University of Maryland’s Center for Vaccine Development in Baltimore.
Initial safety and immune response data should be available by the end of 2016, Dr. Fauci said. If these data are promising, a phase II clinical trial will be launched in early 2017 in several Zika-endemic countries. The NIH has the in-house capability to manufacture the 2,500-5,000 doses of vaccine that the phase II trial is expected to require.
However, said Dr. Fauci, without congressional approval of additional funding for Zika virus vaccine efforts, the transition to a phase II clinical trial is far from certain. Interruption in funding would be “effectively impeding our smooth process on the vaccine development front,” he said. “When I say we are going to run out of money soon, I mean really soon.”
Dr. Fauci, in response to questions, said that he continues to be bullish on such platform-based approaches to vaccines. The DNA strategy, in particular, represents “a very convenient and easily scalable vaccine,” he said. “We are moving much more toward platform-based vaccines … because of their ease and convenience, and scaling up and rapidity.”
The scope of a vaccination program will depend on the endemicity of the virus in a given area, said Dr. Fauci. In an endemic area, “Ultimately, you want to get women of childbearing age, as well as their sexual partners,” he said. This means that target populations will be as young as possible, to make sure women and their partners are vaccinated by the time pregnancy becomes a possibility.
Other Zika virus vaccine development efforts underway at NIAID include a strategy that uses a live attenuated virus, an approach used for a dengue virus vaccine that is currently in a phase 3 clinical trial in Brazil, according to the agency’s website. Dengue and Zika are closely related viruses. Another investigational Zika virus vaccine uses genetic engineering to create a vaccine derived from vesicular stomatitis virus, which infects cattle. This strategy, also used in one approach to Ebola vaccination, is in the pre-clinical stage.