Just one dose of a low-cost vaccine proved safe and
stimulated a strong immune response against the
dengue virus in most participants in an early-stage
clinical trial. With further development, the
vaccine may help ease the burden of dengue fever in
developing countries.
Dengue fever occurs in tropical and subtropical
areas of the world, where it is spread by mosquitoes.
Each year, dengue fever affects 50 million to 100
million people and hospitalizes nearly 500,000,
according to the World Health Organization.
Four related viruses can cause dengue fever: DENV-1,
DENV-2, DENV-3, and DENV-4. Infection with one
results in immunity to that specific virus but not
to the other 3. Studies have found that infection
with one virus type increases the risk for severe
dengue fever from a different dengue virus.
The ideal vaccine, therefore, would be tetravalent—meaning
it protects against all 4 dengue viruses.
In previous work, a research team led by Dr. Anna
Durbin of Johns Hopkins University tested vaccine
candidates against each dengue virus. The vaccines—developed
by scientists at NIH’s National Institute of Allergy
and Infectious Diseases (NIAID)—were live-attenuated
vaccines. These vaccines contain weakened viruses
that don’t cause illness but can still induce an
immune response.
In the new study, the scientists tested tetravalent
combinations of the most effective vaccine
candidates against each of the 4 viruses. The phase
I clinical trial included 112 healthy men and women
ranging from 18 to 50 years old. None had prior
exposure to dengue or other related viruses.
The participants were randomized into 4 groups.
Within each group, 20 people received a single
injection of 1 of the 4 combinations. The remaining
8 received a placebo. The NIAID-funded study
appeared online on January 31, 2013, in the Journal
of Infectious Diseases.
All 4 vaccine combinations successfully produced
immune responses without any serious side effects. A
single dose of one vaccine combination, TV003,
induced an antibody response to all 4 dengue viruses
in 45% of participants and a response to at least 3
of the viruses in 90%.
“What is promising about TV003 is that it elicited
solid antibody responses after just one dose,”
explains NIAID's Dr. Stephen Whitehead, who led
development of the vaccine candidates. “Other
vaccines in development require 2 or 3 injections at
higher doses to achieve similar results.”
The scientists found that differences in side
effects and immune responses correlated with
ethnicity. Additional research to evaluate these
racial differences is now underway. The researchers
are also conducting other studies to develop and
evaluate TV003 further.
TV003's inexpensive production cost—less than $1 per
dose—is critical to its potential use in developing
countries where dengue is prevalent. Manufacturers
in Brazil, India and Vietnam have already licensed
the vaccine technology, called TetraVax-DV, for
production and further evaluation. In addition,
phase II trials are scheduled to begin soon in
Brazil and Thailand.
For more information
Reference: J Infect Dis. 2013 Jan 31. [Epub ahead of
print] PMID: 23329850.
A Single Dose of Any of Four Different Live
Attenuated Tetravalent Dengue Vaccines Is Safe and
Immunogenic in Flavivirus-naive Adults: A Randomized,
Double-blind Clinical Trial.
http://www.ncbi.nlm.nih.gov/pubmed/23329850
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