Researchers Begin Human Trials of New Dengue Vaccine

Researchers at the Johns Hopkins Bloomberg School of Public Health are conducting human clinical trials of three candidate vaccine formulations to prevent dengue fever. The phase 1 trial, which began on July 14 in Baltimore, is the result of more than a decade of vaccine development led by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. NIAID is also funding the clinical trial.

Dengue fever affects between 50 million to 100 million people worldwide every year killing nearly 25,000 annually. The disease is transmitted to humans by the mosquitoes Aedes aegypti and Aedes albopictus and is caused by any of four related viruses known as DENV-1, DENV-2, DENV-3 and DENV-4. Dengue virus typically causes mild fever or no symptoms at all, but some people experience the more severe dengue hemorrhagic fever, which can cause high fever, pain, minor bleeding, a drop in blood pressure and, in some cases, coma or death.

There is currently no licensed dengue vaccine. In addition, the Aedes mosquitoes that spread dengue fever are difficult to avoid since they are most active during the day and thrive in urban environments. “Controlling the mosquito vector can work, but it is very expensive and difficult to sustain,” said Anna Durbin, MD, an associate professor in Bloomberg School’s Center for Immunization Research, who is leading the clinical trials at Johns Hopkins. “A vaccine would be the most cost-effective and efficient way to control the spread of dengue.”

The new vaccine is tetravalent, or four-way, meaning that it protects against all four dengue subtypes. Natural immunity to one subtype of the virus does not protect against the other remaining subtypes. Infection from one virus subtype also increases the risk for developing life-threatening dengue hemorrhagic fever and dengue shock with infection by another subtype.

The vaccine candidate uses a live-attenuated dengue virus, a weakened form of virus designed to trigger an immune response but not cause illness. Volunteers who have never been exposed to dengue were randomly assigned to receive one vaccine formulation or a placebo. The phase 1 portion of the trial will test the vaccine’s safety and measure its ability to stimulate an immune response. Evaluation of a second candidate combination vaccine is being conducted at the University of Vermont in Burlington. A third candidate will be evaluated at the Bloomberg School later this year.

Development of the vaccine was led by Stephen S. Whitehead, PhD, and Brian Murphy, MD, of NIAID's Laboratory of Infectious Diseases. The researchers started by testing seven monovalent vaccines, each of which is designed to protect against a single dengue serotype.

“This study is the culmination of a decade of clinical evaluation, and is an important next step in our efforts to combat dengue fever,” said Ruth Karron, MD, director of the Center for Immunization Research and the Johns Hopkins Vaccine Initiative.

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