The first of five early-stage clinical studies to test the ability of an investigational Zika vaccine candidate––the Zika purified inactivated virus (ZPIV) vaccine––to generate an immune system response has begun at the Walter Reed Army Institute of Research (WRAIR) Clinical Trial Center in Silver Spring, Maryland. Scientists at WRAIR, part of the U.S. Department of Defense, developed the vaccine. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), is cofunding the phase 1 clinical trial at WRAIR, serving as the regulatory sponsor, and providing other support.
The experimental ZPIV vaccine is based on the same technology WRAIR used successfully in 2009 to develop a vaccine for another flavivirus, Japanese encephalitis. The ZPIV vaccine contains whole Zika virus particles that have been inactivated, meaning that the virus cannot replicate and cause disease in humans. However, the protein shell of the inactivated virus remains intact so it can be recognized by the immune system and evoke an immune response.
NIAID partially supported the preclinical development of the ZPIV vaccine candidate, including safety testing and nonhuman primate studies, which found that the vaccine induced antibodies that neutralized the virus and protected the animals from disease when they were challenged with Zika virus. WRAIR, NIAID, and the Biomedical Advanced Research and Development Authority (BARDA) have established a joint research collaboration agreement to support development of the vaccine.
The new study aims to enroll 75 adults (18 to 49 years of age) with no prior flavivirus infection. Flaviviruses include Zika virus, yellow fever virus, dengue virus, Japanese encephalitis virus, and West Nile virus. The participants will be randomly divided into three groups: the first group (25 participants) will receive two intramuscular injections of the ZPIV test vaccine or placebo (saline) 28 days apart; the other two groups (25 participants each) will receive a two-dose regimen of a Japanese encephalitis virus vaccine or one dose of a yellow fever vaccine before beginning the two-dose ZPIV vaccine regimen. Investigators chose to administer additional flavivirus vaccines because U.S. service members are often vaccinated against these diseases before deploying to Zika-endemic areas.
In addition, 30 of the participants who receive the two-dose ZPIV regimen will receive a third dose one year later. All participants in the trial will receive the same ZPIV dose (5 mcg) at each injection. The study is expected to be completed by the fall of 2018.
Four additional phase 1 studies to evaluate the ZPIV investigational vaccine are expected to begin in the coming months. These include:
Source: NIH; November 7, 2016.