The latest dengue vaccine reduced
the occurrence of the disease by about 80 percent in children vaccinated
compared with unvaccinated children, researchers report. But the full picture
of the vaccine’s safety and effectiveness is still under study, and won’t
emerge for several more years.
Dengue is responsible for an
estimated 390 million infections each year. There’s no cure for the viral
disease, which can cause fever, aches, pain and — in severe cases — bleeding, vomiting and rapid loss of blood pressure,
which can be fatal. Young children and the elderly are especially vulnerable to
developing severe disease.
The new vaccine, under development by Takeda Vaccines, is called TAK-003. Among 12,700 children ages 4 to 16 who were given two doses of TAK-003 three months apart, 61 infections occurred, compared with 149 cases among 6,316 children not given the vaccine. TAK-003 also reduced the occurrence of dengue cases that lead to hospitalization by 95 percent: Of the 210 cases of dengue, there were five hospitalizations among the vaccinated children compared with 53 in the unvaccinated ones, researchers report online November 6 in the New England Journal of Medicine. The results describe how the vaccine performed in the year after the second dose; the children, from Asia and Latin America, will continue to be followed another 3½ years.
Dengue, one of the world’s
most rapidly spreading mosquito-borne diseases, is gaining footholds in new areas thanks to global
travel, urbanization and climate change (SN:
10/7/19). Along with measures to control mosquito populations, developing a
vaccine is seen as key to fighting dengue, says Derek Wallace, a physician who
heads the dengue vaccine development program at Takeda Vaccines in Cambridge,
But creating a vaccine
against dengue is challenging. There are four different, but closely related, dengue
viruses, labeled by number. A person infected by dengue type 1, for example, develops
antibodies to that type. But those antibodies can conspire to make a second infection with a different dengue
virus severe (SN: 11/8/17).
This phenomenon, called
antibody dependent enhancement, “plagues vaccine development,” says Scott
Halstead, a virologist who has spent his career studying dengue and first described this enhancement in the 1960s. If a
vaccine doesn’t produce a strong and long-lasting immune response to all four
of the viruses, it could mean a later infection not only isn’t protected
against, but is actually made worse.
That’s what happened with the
first widely used vaccine candidate, Dengvaxia, developed by the pharmaceutical
company Sanofi Pasteur, based in Lyon, France. In a 2015 study, researchers
reported the vaccine reduced the occurrence of dengue by around 60 percent in
vaccinated children. But in 2017, the company announced the vaccine shouldn’t
be used in children who hadn’t been previously exposed to dengue. A huge
vaccination campaign in the Philippines was halted,
and reports surfaced of some children becoming very ill after vaccination (SN: 5/21/19).
“The vaccine was acting as a
silent first infection in those kids who hadn’t been exposed in the past,” says
infectious disease epidemiologist Isabel Rodriguez-Barraquer of the University
of California San Francisco School of Medicine, who was not involved in the
development of either vaccine. After reanalyzing the data from the Dengvaxia
clinical trials, scientists reported that the vaccine protected kids who
already had been exposed to dengue, but increased the risk of severe infections in kids who
hadn’t been, according to a study
published July 2018 in the New England
Journal of Medicine.
Going forward, it will take a lot of
transparency from vaccine manufacturers and questioning from the scientific
community “to make sure that the same thing doesn’t happen again,” Rodriguez-Barraquer
says. “I do hope eventually there will be a dengue vaccine that will be
accepted,” she says. “It would help a lot of people.”
The new vaccine by Takeda uses a
weakened version of dengue type 2 virus as its backbone with bits of the other
dengue viruses added to it. By comparison, the Sanofi Pasteur vaccine was made
with a yellow fever virus that incorporated pieces of each of the dengue
Takeda tested whether children in its
study had been exposed to dengue before vaccination. Initial results didn’t
find a large difference between the groups: The vaccine reduced the occurrence
of disease by close to 75 percent in those not previously infected with dengue,
and by 82 percent in those who had been. But the extent of the vaccine’s
protection won’t be clear until the longer term results are available.