A single-dose dengue vaccine, tested in a small clinical trial, was 100 percent effective in protecting human volunteers from a strain of the most prevalent mosquito-borne virus in the world.
It could represent a major advance in the battle against dengue, which infects nearly 400 million people across more than 120 countries each year. Most survive with few or no symptoms, but more than 2 million annually develop what can be a dangerous dengue hemorrhagic fever. That kills more than 25,000 people each year.
More Tests Underway
Preventing dengue has been a challenge. A three-dose vaccine called Dengvaxia has received limited licensure in Mexico, the Philippines, and Brazil. In its clinical trial, that vaccine produced antibodies against the dengue virus and protected patients during the first year after vaccination.
But two years after, children who were under 9 when vaccinated were hospitalized for dengue at a significantly higher rate than those who received a placebo. For this reason, researchers led by Anna P. Durbin, associate professor in international health at the Bloomberg School, were concerned that measuring antibodies alone may not truly indicate the ability of the vaccine to protect against dengue.
Based on Durbin’s new findings, researchers in Brazil have begun administering the new single-dose vaccine in a large Phase 3 clinical trial designed to look at vaccine efficacy against naturally occurring dengue.
“Knowing what we know about this new vaccine, we are confident that it is going to work,” Durbin says. “And we have to be confident: Dengue is unique and if you don’t do it right, you can do more harm than good.”
Protect Against All 4 Strains
Dengue can cause a high fever, severe headaches, severe pain behind the eyes, rash and joint, muscle or bone pain. Dengue hemorrhagic fever occurs when blood leaks from blood vessels into other parts of the body, which can lead to failure of the circulatory system and shock, and possibly death, without prompt, appropriate treatment.
Four very different strains of dengue circulate, so a successful vaccine must prevent all four. It has long been known that people who are infected with one dengue virus are likely to get sicker if they are infected a second time with a different strain.
The new TV003 vaccine, as it is called, was already known to be good in preventing dengue 1, 3 and 4 viruses, but the portion designed to prevent dengue 2 did not induce as strong an immune response in people as the other three components. So the researchers decided to see if the vaccine could specifically protect against the dengue 2 virus if people were exposed six months after being vaccinated.
For this study, instead of looking only at antibodies, the researchers looked for the evidence of actual infection: virus in the blood, rash and low white blood cell count.
Vaccine for Zika?
Researchers from the Bloomberg School and the University of Vermont administered TV003 or a placebo to healthy adult volunteers. Six months later, 41 participants were exposed to dengue 2 virus.
None of the 21 who had received the vaccine developed any evidence of infection in their blood, nor did they develop rashes or have low white blood cell counts. In contrast, all 20 placebo recipients developed virus in their blood, 80 percent developed rashes, and 20 percent had low white cell counts.
Only a single dose was necessary.
Researchers believe the vaccine’s effects will be long-lasting, though they only tested it after six months.
Durbin, who has been working on a dengue vaccine for more than 15 years, says the methods used in this study could be the basis for developing a vaccine against Zika, a mosquito-borne infection in the same virus family as dengue.
Beth D. Kirkpatrick, Stephen S. Whitehead, Kristen K. Pierce, Cecilia M. Tibery, Palmtama L. Grier, Noreen A. Hynes, Catherine J. Larsson, Beulah P. Sabundayo, Kawsar R. Talaat, Anna Janiak, Marya P. Carmolli, Catherine J. Luke, Sean A. Diehl, Anna P. Durbin
The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model
Science Translational Medicine16 Mar 2016 : 330ra36
Photo: PATH global health via Flickr