NIH Launches Phase 1 Dengue Vaccine Trial

From Medscape Medical News

Martha Kerr

August 10, 2010 — The National Institutes of Health announced today that phase 1 testing of a vaccine against the mosquito-borne dengue virus has begun.

The vaccine was developed at the National Institute of Allergy and Infectious Diseases (NIAID), and phase 1 testing is taking place at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.

The new vaccine is tetravalent, incorporating all 4 dengue viruses — DENV-1, DENV-2, DENV-3, and DENV-4 — transmitted by Aedes mosquitoes. Someone with antibodies against only 1 or a few of the virus serotypes is actually at higher risk of developing a severe form of the disease, researchers say.

Development of the tetravalent live-attenuated vaccine at NIAID was led by Stephen S. Whitehead, PhD, and Brian Murphy, MD, who started by testing 7 monovalent vaccines. "Our overall strategy was to identify the best individual candidate for each serotype, based on safety and ability to induce an immune response, and to then combine those into a tetravalent vaccine," Dr. Whitehead said in an NIAID release announcing the launch of clinical testing of the vaccine.

Evaluation of a second candidate combination vaccine is taking place at the University of Vermont in Burlington. Trials of a third are scheduled to begin soon at Johns Hopkins. These early clinical trials are designed to test the safety and immunogenicity in healthy adults 18 to 50 years of age.

Volunteers will receive 1 dose of the assigned vaccine or placebo and will be monitored for 6 months. After determining which tetravalent vaccine is most promising, the researchers will test that candidate in a trial in a new group of volunteers in Brazil, where dengue is highly prevalent.

Phase 2 testing will include both unexposed subjects and those previously infected with dengue, and will evaluate the need for a booster shot within a few months of the initial vaccination.

"If everything goes well after that stage, we hope to start the final phase of human testing in 3 to 4 years," said Johns Hopkins lead investigator Anna Durbin, MD. "Controlling the mosquito vector can work, but it is very expensive and difficult to sustain," she pointed out. "In the long run, vaccination would be a more efficient and cost-effective approach."

Dengue virus is prevalent in tropical and subtropical regions of the world, and each year infects about 50 million to 100 million people. There are approximately 25,000 deaths annually, most of them in children. About 2.5 billion people in more than 100 countries worldwide live in endemic areas, and the prevalence is increasing.

"This is an important milestone for NIAID's intramural scientists in the development of a model dengue vaccine, which could potentially have a major impact in preventing dengue," says NIAID director Anthony S. Fauci, MD. "With increasing infection rates and disease severity around the world and the discovery of dengue in parts of Florida, finding a way to prevent dengue infection is an important priority."

For more information, see NIAID's Dengue Fever portal.