An experimental dengue vaccine, TV003 that was developed by Dr. Whitehead and his colleagues at NIAID’s Laboratory of Infectious Diseases along with scientists from the U.S. Food and Drug Administration Center for Biologics Evaluation and Research protected 100% of the vaccine recipients in a clinical trial.
Volunteers in this trial were infected with dengue virus six months after receiving either the experimental dengue vaccine TV003 or a placebo injection. All 21 volunteers who received the vaccine, were protected from dengue infection, while all 20 placebo recipients developed dengue.
“The findings from this trial are very encouraging to those of us who have spent many years working on vaccine candidates to protect against dengue, a disease that is a significant burden in much of the world and is now endemic in Puerto Rico,” said Stephen Whitehead, Ph.D., of NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
“In fact, 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.”
This study also underscores the importance of human challenge studies, in which volunteers are exposed to disease-causing pathogens under carefully controlled conditions.
The candidate vaccine is a live, attenuated vaccine meaning it was made from a mixture of four live, weakened (attenuated) viruses targeted to each of the four serotypes of dengue. A total of 48 healthy adult volunteers enrolled at two trial sites, the University of Vermont College of Medicine, Burlington, and Johns Hopkins Bloomberg School of Public Health, Baltimore, and were randomly assigned to receive either the attenuated vaccine or placebo injection.
Six months later, 41 people returned for the challenge with dengue virus. After the secondary infection with the “challenge virus” to check the efficacy of the vaccine, results showed that none of the 21 TV003 vaccine recipients developed viremia or any other sign of infection after challenge. However, all 20 placebo recipients developed viremia, 16 (80 percent) developed mild rash and 4 (20 percent) had a temporary drop in white blood cell count following challenge with the virus.
The virus which was used as the “challenge virus” in the trial was a genetically modified version of a dengue-2 serotype virus which was originally noted for causing only mild illness. It led to viremia (showed presence of virus in blood) but other than that most humans developed just a mild rash. By inducing only rash (without fever) in the majority of recipients, the challenge virus mimics natural dengue virus infection, which often features such a rash, Dr. Whitehead noted.
A human challenge model of dengue infection—rather than illness—is an important characteristic, explained Anna Durbin, M.D., who led the clinical trial at Johns Hopkins. She further added, “The reliably high percentage of those who develop viremia following exposure to this challenge virus is another advantage—when most or all volunteers develop viremia or other signs of infection, clinical trials can enroll relatively small numbers of people but still achieve answers to such questions as whether a candidate vaccine protects against infection.”
Dengue virus is in the same virus family as Zika virus and both are primarily spread by the Aedes mosquito, and the NIAID team is now leveraging their experience with the live-attenuated dengue vaccine in efforts to develop a Zika vaccine, Dr. Whitehead noted.