feature
“We need a better
understanding of the different
immune mechanisms and how they
can protect against the virus.”
—Jackie Katz, PhD
Seeking A True Game Changer
The holy grail of influenza prevention
and control is a universal flu vaccine
that would provide long-term immunity
against all influenza viruses. And that
is still a “good way off,” said Jackie
Katz, PhD, head of the CDC-based WHO
Collaborating Center for Surveillance,
Epidemiology and Control of Influenza.
Instead, current influenza vaccines are
strain-specific, targeting the viruses
projected to predominate six to nine
months or so after WHO issues its vaccine
recommendation for the Northern
Hemisphere in February and for the
Southern Hemisphere in September.
Those recommendations are based on a
painstaking review of “over a thousand
pages” of antigenic, genetic and other
data from WHO collaborating centers
and partners, including mathematical
modelers. Yet it is always a gamble.
Katz said, “Current vaccines are based
on an understanding of one type of
immunity—a neutralizing antibody
directed against the head of the
hemagglutinin.” And that spiky protein
head, she said, “is a moving target,”
subject to continual change (“antigenic
drift”) as a result of mutations that
occur while the virus resides in host
organisms and while it is grown in
chicken eggs during the months-
long vaccine production process.
“I think in most years we’ve had a good
antigenic match,” said Katz. “But we’ve
been wrong five times in the last 25 years
for the H3N2 subtype, the most variable
human influenza A virus, with the most
recent mismatch in the 2014-15 season.”
To up the odds of success, WHO
authorities have begun issuing
recommendations for the traditional
trivalent (three-strain) vaccine, plus
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LAB MATTERS Winter 2018
a quadrivalent (four-strain) vaccine.
Thus, today 75% of US flu vaccines are
quadrivalent, including two strains of
influenza B (one from the Yamagata
lineage and one from the Victoria lineage)
and two strains of influenza A (typically
an H3N2 virus and an H1N1 virus).
In addition, some years ago, the US
Biomedical Advanced Research and
Development Authority (BARDA)
jumpstarted an effort to grow influenza
viruses in cell culture to avoid the
genetic and antigenic changes that may
be introduced into egg-based vaccines.
BARDA also invested in bringing a
recombinant flu vaccine to the market,
another non-egg-based technology.
But to achieve a true game-changer—a
universal vaccine—scientists must think
outside the box.
“We need a better understanding of the
different immune mechanisms and how
they can protect against the virus,” said
Katz. “The strategy is to focus vaccine
response on something that doesn’t
change as much [as hemagglutinin].”
So far, she said, “We’re still just
scratching the surface.”
In some ways, the 1918 pandemic was
unique. Nearly half the flu-related
deaths were in adults 20–40 years of
age, and more than 99% were among
those under age 65. The virus attacked in
three waves within a 12-month period.
And WWI conditions—overcrowding,
mass movements of civilians and
military personnel, and reluctance
to shut down wartime production
facilities—worked in the virus’s favor.
“Today we have vaccines,