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FORTUNE.COM // DECEMBER 2019
were more likely to be hospitalized.
Children ages 2 to 5 who received Dengvaxia
in the company’s Phase III trial were, in fact,
more than seven times as likely to be hospital-
ized for dengue as those who had not. The
overall numbers were small: 19 children of the
3,598, or 0.6% of kids age 2 through 8 who
were vaccinated, were hospitalized owing to
dengue versus 0.4% in the control population.
The data did not show the same risk for vac-
cinated children ages 9 and above, however.
The researchers didn’t have definitive con-
clusions to explain the trend, but they posited
a few theories that related to age (younger
started studying the virus in 1957, when he
was a young Army doctor stationed in Asia.
His career coincided with dengue’s flourish-
ing, and one way or another, he’s had a hand
in many of the foundational and pivotal find-
ings in the field.
It was Halstead who opened Asia’s first
dengue laboratory. He was in Bangkok (in the
1960s) to help develop the standards of den-
gue diagnosis and case management. He was
in a lab in New Haven (in the 1970s) to study
the pathogenesis of dengue infections in mon-
keys. And he was in Cuba (in the 1980s) to
help study the first-ever dengue hemorrhagic
fever epidemic in the Americas, and in Geneva
(in the 1990s) to help establish the WHO’s
dengue case classification system that Sanofi
used in its Dengvaxia trials. Halstead founded
the Pediatric Dengue Vaccine Initiative (later,
DVI), an organization that received $55 mil-
lion in Gates Foundation funding in 2003.
But perhaps Halstead’s signature if contro-
versial contribution is “antibody-dependent
enhancement,” the theory he developed in the
1970s—based in part from his study of dengue
in monkeys—that aims to explain why people
typically get more sick the second time they
get dengue.
Halstead had been enlisted by Sanofi as a
consultant on Dengvaxia. He says he flew to
Paris for meetings a few times but found them
pointless: “We never discussed anything!”
Still, he says, he didn’t anticipate problems
with the vaccine. Halstead believed Dengvaxia
had gotten around the problem of antibody-
dependent enhancement by exposing people
to all four strains at once. But as he pored over
the new data in the New England Journal
study about higher hospitalization rates of
younger vaccinees, he had a sinking feeling.
Halstead says he knew instantly that he had
been wrong. He was sure this was his old
theory in action: For those who hadn’t been
exposed to the virus, the vaccine acted like
a first dengue infection, priming them for a
potentially more severe infection when they
later got dengue from a mosquito bite.
In February 2016, two months before
the Philippines launched its school-based
Dengvaxia program, Halstead and a former
colleague published an article in the medi-
cal journal Vaccine warning that people not
previously exposed to dengue would be at
risk of a more severe case later if vaccinated.
(He’s since written more than a dozen papers
outlining issues related to Dengvaxia.)
Halstead’s argument didn’t sway Sanofi,Sanofi Pasteur
executives,
Thomas Triom-
phe (right) and
Yu Tan-Wen,
testifying on
Dec. 11, 2017,
at the Philippine
Senate probe
into the govern-
ment’s Dengvaxia
immunization
program.children were not as physically and im-
munologically robust) and serostatus—that
is, whether or not the child had suffered a
previous dengue infection. In the best-case
scenario, Sanofi would have marketed the
vaccine to kids as young as age 2. The data
analysis made that impossible. From now
on, only children as old as 9 would be given
the drug.
When Scott Halstead read the New
England Journal report in the summer of
2015, he says, he nearly fell off his chair.
Halstead, now 89, is a towering figure
in the dengue research community. He^