By Dennis Normile
As scientists and public health offi- cials mull over the puzzling results of the first large efficacy trial of a vac- cine for dengue, one thing is clear: “There are complexities we’ve never seen in any other vaccines,” says
Annelies Wilder-Smith, a public health specialist at Nanyang Technological University
(NTU) in Singapore.
The vaccine, the fruit of decades of public and private sector efforts, reduced the
incidence of the mosquito-borne disease
overall by 56.5% and, perhaps more significant, cut cases of dengue hemorrhagic fever, a severe form of the disease, by 88.5%.
But the vaccine provided only limited pro-tection against dengue 2, one of the four
serotypes of the virus, and, mysteriously,
it worked best in people who had already
recovered from one dengue infection and
among older children.
Reported online on 11 July in The Lancet,
these results will likely leave public health
officials in dengue-endemic countries grap-
pling with whether to include the Sanofi
Pasteur vaccine in national immunization
programs. Its cost, the logistics of deliver-
ing three doses over the course of a year,
and its limited efficacy in regions where
the dengue 2 serotype predominates must
all be considered. And because the vaccine
works best in preventing second infections,
its value in subtropical nations where den-
gue is not yet firmly entrenched is even
more questionable. Joachim Hombach, se-
nior adviser to the World Health Organiza-
tion (WHO) on immunization and vaccines
in Geneva, Switzerland, says the results can
“clearly translate” into public health ben-
efits. But each country will have to care-
fully study the costs, risks, and benefits in
light of its own epidemiological situation,
he adds.
No one ever thought developing a vac-
cine for a disease as complicated and poorly
understood as dengue would be easy. The
four virus serotypes, all spread by the Ae-
des aegypti mosquito, are found through-
out the tropics, but one strain or another
often predominates in different regions
and at different times. A first infection with
any of the serotypes typically causes a mild
fever, rash, and muscle and joint pain. Pa-
tients then have lifelong immunity to that
serotype. But infection with a second sero-
type raises the risk of a little-understood
phenomenon called antibody-dependent
enhancement, which can cause dengue
to $600,000 a year (plus another 50% for
overhead costs) that will replace an inves-
tigator’s project-based grants. (NIH’s aver-
age R01 covers $282,000 a year in direct
costs for 4.3 years.) NCI expects that if it
adds 50 of these Outstanding Investigator
Awards a year for 7 years, the program will
total $317 million a year, or about 16% of
the $2 billion that NCI now spends on re-
search grants.
At NIGMS, a people award would replace
a standard NIGMS project grant, offering
$150,000 to $750,000 a year in direct fund-
ing for 5 years. But Lorsch says that un-
like NCI and HHMI awards, the so-called
Maximizing Investigators’ Research Award
his institute plans to pilot-test would be
intended not just for high-risk research or
for “a perceived elite,” but also for “regular
outstanding researchers.”
Several other NIH institutes are also
planning people awards, Rockey says. But
other funders’ experiences could make
them cautious. For example, NIH Direc-
tor Francis Collins noted in a meeting ear-
lier this month that the United Kingdom’s
Wellcome Trust, which 3 years ago shifted
roughly $180 million in annual project
grant funding to people awards (Science,
13 November 2009, p. 921), is now “re-
thinking” the program. Collins says Well-
come officials are concerned about the
“graying” of its investigators—one risk of
basing awards on reputation. Asked for
comment, a Wellcome Trust representative
pointed to a blog post last week from Di-
rector Jeremy Farrar saying that he plans
to increase opportunities for early- and
mid-career investigators.
Lorsch says NIGMS will give early-stage
investigators a boost by judging them
through a separate review process that will
examine their graduate and postdoctoral
records; the institute may also set targets
to make sure enough young investigators
are funded. But Rockey raises another concern: As an institute funds more long-term
awards, the amount of money that turns
over each year will go down, which could
mean fewer awards overall. Institutes will
“need to balance their portfolios,” she says.
Howard Garrison, deputy executive director for policy at the Federation of American Societies for Experimental Biology in
Bethesda, Maryland, said his group’s members are still discussing NIH’s plans. “I
suspect that views will be mixed,” he says,
citing “concern about how funding ‘people
instead of projects’ will affect younger
scientists.” But he adds: “More and more
people are frustrated by the continuous
struggle for funding, and there is a growing acceptance of the idea that we need to
do something different.” ■
SCIENCE
sciencemag.org
P
H
OT
O
:
S
A
N
O
F
I
PAST
E
U
R
/
F
L
IC
K
R
Dengue vaccine trial poses
public health quandary
Experimental vaccine fell short against key strain
TROPICAL DISEASES
25 JULY 2014 • VOL 345 ISSUE 6195 367
A pediatric trial
of a dengue vaccine
produced mixed results.
