Forty one individuals were voluntarily infected with the dengue virus in a new vaccine (TV003) clinical trial, which proved 100% successful. Volunteer safety is a priority in all human trials; such trials would not be conducted with deadly infectious agents, such as Ebola or HIV.
According to the World Health Organization (WHO), there are 4 different, but closely related dengue viruses, or serotypes
: DEN-1, DEN-2, DEN-3 AND DEN-4, which affect most of the Asian and Latin American communities, and, more recently, Hawaii
. Infection and treatment of one virus renders an individual immune to that serotype alone, although temporary cross-immunity is possible. Infection with more than one serotype may result in severe dengue complications.
Dengue Vaccine Development
Dengue vaccine, TV003
, was developed mainly by the National Institute of Allergy and Infectious Disease (NIAID) scientist, Dr. Whitehead, with the help of fellow researchers from NIAID’s Laboratory of Infectious Diseases, as well as US Food and Drug Administration (FDA) Center for Biologics Evaluation and Research scientists. Due to the large number of previously infected individuals, it is difficult to determine which serotype a person is immune to, and so the vaccine is composed of four live but attenuated viruses, each targeting one of the serotypes spread by the female Aedes aegypti
Human Dengue Vaccine Trial
, published in Science Translational Medicine
, enrolled volunteers for the clinical trials at one of two sites: University of Vermont College of Medicine in Burlington, VT and John Hopkins Bloomberg School of Public Health in Baltimore, MD. The volunteers were randomly placed into one of two groups to receive either the vaccine or the placebo injection. The vaccine used in the human trials was composed of a modified version of a DEN-2 serotype, known to only cause mild illness. Previous trials using this modified serotype determined the viral dose which would trigger the presence of the virus within the blood while only causing mild rash, and no fever, simulating a natural dengue infection. Co-first author, Stephen Whitehead, PhD, explained that this modified serotype has proven to be very advantageous in that it can replicate dengue infection in a large number of volunteers without being harmful.
None of the individuals inoculated with the TV003 vaccine used in the trail presented with viremia, while all 20 members of the control group developed viral presence in their bloodstream. Symptoms of infection within the control group ranged from mild rash (80%), to a transient decrease in white blood cell count (20%).
Commenting on the outcome of the trial, Dr. Whitehead stated, “We were pleasantly surprised to see that this candidate vaccine provided complete protection in everyone who received it…The dengue-2 serotype is considered the relatively weaker component in this, and other, candidate dengue vaccines, so its ability to confer protection from a challenge with dengue-2 virus was encouraging…These results informed the recent decision by officials at Brazil’s Butantan Institute to advance the TV003 vaccine into a large phase 3 efficacy trial
Development of a human trial which will utilize a DEN-3 serotype is underway. Dr. Whitehead hopes that this challenge serotype can be used to test the effectiveness of candidate dengue vaccines, or even therapies. In addition, Dr. Whitehead and other NIAID scientists hope that the success of this trial can aid in the development of a Zika vaccine, in the near future.
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