Testing of Investigational Zika Vaccine Begins in Humans

First of five planned clinical trials

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:

  • A study involving 90 adults (18 to 49 years of age) at the Center for Vaccine Development at the Saint Louis University School of Medicine. The participants will receive either two injections of ZPIV or placebo 28 days apart. The participants will be randomly assigned to receive a high, moderate, or low dose at both injections to evaluate the optimal dose for use in larger future studies.
  • A study of 90 adults (21 to 49 years of age) at Ponce Health Sciences University in Puerto Rico. This trial will examine the vaccine’s safety and immunogenicity in participants who have already been naturally exposed to dengue virus. The participants will be randomly assigned to receive a high vaccine dose, a moderate vaccine dose, or placebo.
  • NIAID’s Vaccine Research Center will test the ZPIV vaccine candidate as a booster vaccination to its DNA Zika vaccine candidate, which entered phase 1 clinical trials in August. The next part of the study, which will enroll 60 additional participants aged 18 to 50 years, will be conducted at the NIH Clinical Center in Bethesda, Maryland; at the Center for Vaccine Development at the University of Maryland School of Medicine’s Institute for Global Health in Baltimore; and at Emory University in Atlanta. Half of the participants will receive the NIAID Zika virus investigational DNA vaccine followed by a ZPIV vaccine boost four or 12 weeks later. The remaining participants will receive two doses of ZPIV vaccine four or 12 weeks apart.
  • A WRAIR-funded trial involving 48 adults (18 to 50 years of age) will be conducted at the Center for Virology and Vaccine Research, part of Beth Israel Deaconess Medical Center, and Harvard Medical School in Boston. One group of participants will receive a single dose of the ZPIV vaccine, and the remaining participants will receive two doses of the ZPIV vaccine at varying intervals.

Source: NIH; November 7, 2016.