114
FORTUNE.COM // DECEMBER 2019
about the virus in the early 1950s remain
unanswered today. “Half of the world lives at
daily risk of being infected with dengue,” says
Thomas, “but we don’t know why some people
get sick and some people don’t. We don’t
know why some people get very sick and some
don’t. A lot of the questions that have plagued
dengue researchers are the exact questions
that have been so problematic to vaccine
developers.” There’s not an animal model that
comprehensively mimics the disease in hu-
mans, explains Thomas, who has been a paid
adviser to numerous dengue vaccine develop-
ers, including Sanofi.
What we do know about dengue is that it’s
insidiously complicated. Its basic epidemiol-
ogy reads like a Mensa logic problem.
Dengue virus comes in four similar but
distinct varieties, known as Dengue serotypes
1 through 4. When individuals get a first den-
gue infection, they develop lifelong immunity
from the infecting strain. For a brief period
of time, they also enjoy protection from the
other three. But that cross-protection wears
off—after a period of anywhere from two
months to two years—and the individual
becomes vulnerable to getting more severely
ill on a second infection.
That’s why it’s the second infection that
health officials worry about. People tend to get
only mildly sick or not sick at all after their
first dengue infection, and for some reason,
they hardly ever get sick on their third or
fourth. The worst, life-threatening cases of
dengue, the ones with plasma leakage that can
lead to hemorrhagic fever or shock, almost
always result from a second exposure.
To make matters more complicated, all
four serotypes are constantly comingling in
most dengue-endemic countries, meaning the
chances are higher for a second infection to
occur. (So is the likelihood of a genetic muta-
tion, which could produce a more virulent
virus.) That wasn’t the case in most places
even a couple of decades ago, and it helps
explain why the number of dengue cases
has risen so dramatically. Given these facts,
virologists decided that the best strategy for
beating dengue, along with mosquito control,
was to develop a tetravalent vaccine—one that
provided balanced protection, in the form
of neutralizing antibodies, against all four
serotypes.
That’s what Sanofi was going for inAn employee
working on a
vaccine assem-
bly line in Sanofi
Pasteur’s vaccine
production facil-
ity outside Lyon.