Pathogens and People: A universal flu

vaccine?
By EDWARD McSWEEGAN, For The Capital
Published 12/06/09

It's flu season and the hunt is on for some vaccine. I found this year's seasonal flu vaccine
at work. My daughter found the H1N1 swine flu vaccine at school. My wife may get
some H1N1 through Anne Arundel County. My son hasn't had either vaccine yet. It's a
mad scramble for flu vaccines made worse this year by the sudden appearance of a novel
H1N1 influenza strain to which few people have any immunity.

Normally, the influenza season is preceded by months of worldwide surveillance for

emerging flu viruses, followed by mass-production of a three-virus vaccine designed to
prevent the spread of the most important of those circulating flu viruses. It is part crystal-
ball-gazing and part Rube Goldberg vaccine production that is ultimately dependent on
chickens laying millions of eggs so viruses can be grown in those eggs. It is a 50-year-old
technique that is cumbersome and expensive, and made all the more so by the dearth of
companies interested in making these unprofitable vaccines. (In 1988, there were 25
vaccine makers in the U.S. Today there are four. Of the three U.S. companies making flu
vaccine, two are relying on overseas facilities.)

The appearance of a novel pandemic flu virus has complicated the normal vaccine
production schedule and strained the few worldwide facilities able to make such a
vaccine. Now there is a shortage of swine flu vaccine in the U.S. The manufacturers are
being blamed for making promises they could not keep. The federal government is being
blamed for believing the manufacturers. The public is blaming the government for its
optimistic pronouncements and contradictory messages. David Fidler, a health law expert
at Indiana University, suggested to The Washington Post and Science magazine that one
casualty of this year's flu season may be the government's credibility.

Can this kind of epidemiological, commercial and political chaos be prevented in the
future? Maybe. First, we have to stop relying on chickens and eggs, and start making
influenza vaccines in clean, controlled cell culture systems. Second, we have to think
about making a universal flu vaccine.

The influenza virus is a shifty character that changes its appearance on a regular basis. On
its surface are two important proteins called hemagglutinin (HA) and neuraminidase
(NA). The virus needs these proteins to infect our cells and cause influenza. To protect
them from our patrolling immune systems, the virus regularly makes subtle (and
occasionally drastic) changes to their appearance. Imagine being in a crowded shopping
mall and trying to spot a bespectacled man in a red jacket who has ditched his glasses and
jacket. That is what our immune systems are up against each flu season as the virus sheds
a recognized HA and NA for slightly different ones.
Suppose instead of concentrating solely on the glasses and red jacket of our imaginary
mall walker, we also remember to look for his slight limp, prominent nose and blond hair.
Those are helpful additional clues for spotting our quarry. Similarly, the influenza virus
carries other recognizable features that our immune systems can spot. One of these is a
channel protein called M2e.

M2e is not as immunologically prominent as HA and NA, but it has the virtue of being
"highly conserved." That is, it doesn't change its shape or structure from year to year.
Antibodies made against last year's influenza M2e protein will recognize this year's
influenza M2e protein. So an M2e vaccine could eliminate the annual international
scramble to spot new influenza viruses and try to make matching vaccines.

Such a universal flu vaccine has already been tested in Phase 1 safety trials. Last year 60
adults received an experimental M2e vaccine manufactured by the biotech company
VaxInnate. The vaccine proved to be both safe and effective in raising an immune
response in the vaccine recipients. Additional trials are under way.

A vaccine like M2e would induce "heterosubtypic" immunity: that is, immunity to a
number of different influenza subtypes. Probably, that kind of immunity would not be as
good as a perfectly matched vaccine to the highly immunogenic HA and NA influenza
proteins. Still, a universal vaccine could be expected to reduce the spread of influenza,
reduce the severity of flu cases and prevent deaths, which is what the current flu vaccines
are intended to do. A universal vaccine also would have the advantage of being produced
in a reliable fashion, and eliminate annual concerns about the quality and quantity of each
newly concocted vaccine formulation.

For those reasons, the pursuit of a universal flu vaccine continues to be a worthwhile
public health goal.

Dr. Edward McSweegan has a Ph.D. in microbiology and lives in Crofton. He works on
and writes about infectious disease issues. He may be contacted at
mcsweegan@nasw.org.