The University of Miami Miller School of Medicine will soon begin one of the nation's first full-scale Zika vaccine clinical trials testing the National Institutes of Health's (NIH) experimental DNA-based vaccine. As Miami-Dade County has been ground zero for the Zika virus outbreak in the U.S., testing the vaccine in an endemic region is critical to help determine the vaccine's safety, effective dosage and whether it can effectively prevent disease caused by Zika infection.
The Miami arm of the NIH study will be led by Margaret Fischl, M.D., a renowned UM infectious disease physician and scientist with the University of Miami Health System and Miller School.
"The vaccine is really important in Miami because we saw the nation's first cases of locally-acquired Zika, which needed a more immediate response," said Fischl, a professor of medicine, Director of the HIV/AIDS Clinical Research Unit, and co-director of the Miami Center for AIDS Research, who was also instrumental in testing the first influenza vaccine. "A Zika vaccine was an important effort to respond to the Zika outbreak."
Researchers will initially recruit individuals from Miami-Dade County, who will be given the vaccine in varying dosages to test safety. The second part of the study, called part B, aims to determine if the vaccine can effectively prevent disease caused by Zika infection. Part B will enroll residents who have not had Zika infection previously from the "Zika zone" neighborhoods where local transmission of Zika occurred. Half of the participants in part B will receive the vaccine and half will receive a placebo. Neither the study investigators nor the participants will know who receives the investigational vaccine.
UM is one of three sites in part A and one of 11 sites in part B. The other part A sites are located in Houston and Puerto Rico. The other sites in part B are located in Houston, Puerto Rico, Costa Rica, Peru, Brazil, Panama and Mexico.
Part A will enroll 90 healthy men and non-pregnant women ages 18-35 years, and part B will enroll 2,400 men and non-pregnant women ages 15-35 years. The vaccine was developed by government scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. NIAID is leading the trial.
Most people with Zika infection have either no or only mild symptoms, such as fever, rash, joint pain, and conjunctivitis (red eyes). However, when Zika infection occurs during pregnancy, the pregnant woman can pass the virus to her fetus, which can result in a range of fetal defects known collectively as congenital Zika syndrome. Currently there is no licensed vaccine to prevent disease caused by Zika infection, which is mainly transmitted via the bite of infected Aedes aegypti mosquitoes but also can be transmitted sexually.
Scientists at NIAID's Vaccine Research Center (VRC) developed the NIAID Zika virus investigational DNA vaccine. It entered early-stage human testing in 2016 following extensive testing in animal models. Initial findings indicate the vaccine is safe and able to induce a neutralizing antibody response against Zika virus. The Phase 2/2b trial aims to gain more safety and immune response data and determine if this immune response protects against disease caused by natural Zika infection.
The Zika vaccine platform is based on a strategy VRC scientists used previously to develop a West Nile virus vaccine candidate. The Zika vaccine candidate contains a single circular strand of DNA called a plasmid into which is inserted genes that encode two proteins found on the surface of the Zika virus. Once injected into muscle, the proteins assemble into particles that mimic Zika virus and trigger the body's immune system to respond. The vaccine does not contain infectious material, so it cannot cause Zika infection.
The trial is being led by protocol co-chairs Julie E. Ledgerwood, D.O., chief of VRC's Clinical Trials Program, and Grace L. Chen, M.D., deputy chief of the same program.
Part B participants will be followed for nearly two years, during which time they will undergo assessments for adverse events and symptoms of Zika infection. Trial participants in both parts will be counseled on how to protect against Zika infection. Investigators will compare the rates of confirmed cases of Zika in the placebo group and the vaccinated group to determine if the investigational vaccine protects against disease caused by Zika infection.
Each site will have a principal investigator responsible for ensuring daily review of safety data as they become available. A protocol safety review team that includes the protocol chairs and other medical officers at NIAID will review safety data reports weekly. The NIAID Intramural Data and Safety Monitoring Board will also review cumulative study data at least twice per year. The study is currently expected to be completed by 2019.