The mosquitoes are gone and winter is upon us, but dengue vaccine testing is heating up at the University of Vermont.

Dengue, commonly considered a disease of tropical and subtropical countries, was confirmed on U.S. soil – in Key West and Miami Beach, Florida – within the last year. According to an October 6, 2010 Journal of the American Medical Association "Medical News & Perspectives" article about the new trials, the World Health Organization (WHO) estimates that 2.5 billion people worldwide are at risk of contracting the deadly virus. Responsible for 22,000 deaths annually, most of which are children, dengue infections number 50 million to 100 million annually, according to WHO. While there is currently no vaccine to prevent dengue fever, a series of phase 1 clinical trials funded by the National Institutes of Health (NIH) was recently launched at two Johns Hopkins University sites and the University of Vermont’s (UVM) Vaccine Testing Center and is examining new tetravalent vaccine formulations against dengue infection.

Transmitted by mosquitoes, dengue infection can be caused by any one of four related, but distinct, dengue serotypes: Dengue viruses 1 through 4. Classically described dengue fever includes fever, headache, severe joint and muscle pain, and rash. Severe dengue infections, dengue hemorrhagic fever, and dengue shock syndrome include a higher risk of complications and death and are more commonly seen after a second infection with dengue viruses.

Since beginning a five-year research collaboration with NIH/National Institute of Allergy and Infectious Diseases and the Johns Hopkins Bloomberg School of Public Health in 2009, Beth Kirkpatrick, M.D., UVM associate professor of medicine and director of the Vaccine Testing Center, Kristen Pierce, M.D., assistant professor of medicine, and colleagues thus far had been testing multiple formulations of monovalent – or single serotype – dengue vaccine.

"This is an exciting step forward, since work on the monovalent components of a live attenuated 4-serotype vaccine has been progressing for years and now we are finally working on what is needed in the field – the combination product or tetravalent vaccine," said Kirkpatrick.

This new series of phase 1 trials is designed to test the tetravalent vaccine’s safety and effectiveness in stimulating immune responses in healthy study volunteers, ages 18 to 50, who have never been exposed to dengue or related viruses. Launched in the summer of 2010, the UVM arms of the trial are examining the effectiveness of three 4-serotype combination vaccines, and hope to find a combination that protects volunteers equally against all four dengue serotypes. All immune responses to the vaccinations, including neutralizing antibody testing, are performed in the laboratories at UVM. As part of the clinical trials, study volunteers are randomly assigned to receive one of the live-attenuated (harmless or less virulent version of the virus) experimental tetravalent vaccine formulations or a placebo. Study participants attend follow-up visits over the course of six months that involve health and dengue symptom assessments, as well as blood and urine sample collection and analysis. The most promising version of the vaccine will be further tested for efficacy in countries endemic for dengue.

UVM co-investigators on the trial include Caroline Lyon, M.D., assistant professor of medicine, and Ann Fingar, M.D., assistant professor of medicine. For more information about the UVM dengue fever vaccine studies, call (802) 656-0013 or email vaccinetestingcenter@uvm.edu. To link to more information about the national trial, visit: Dengue Vaccine Trial.