Fortune Favors the Prepared Immune System
Or, Why You Should Get a Flu Shot
Every year, influenza comes in November, peaks in late February or
early March, and then subsides to a low but steady number of cases. The
Centers for Disease Control (CDC.gov/influenza) collects and studies
influenza viruses from patients in all states to find out which versions of
the virus are circulating. The influenza virus evolves rapidly and
spreads quickly so the CDC effort is important for predicting the
severity of the outbreak, learning how well the existing vaccine or drugs
will cope with it, and for predicting what the next year will bring. Some
years the response to a vaccine is good; some years it is disappointing.
You might think we would be doing better by now.
Influenza viruses are lipid shells containing RNA instructions for
making new viruses. (RNA is a slight variant of DNA, often used by
viruses.) Poking out of the viral spheres are two spike-shaped proteins,
Hemaglutinin and Neuraminidase, abbreviated H and N. H and N vary
every year. There are 16 forms of H and 9 forms of N among the various
flu viruses that infect humans, birds, pigs, bats or other animals.
Flu is deadly because of its enormous variability. In the population of
flu viruses around the world, there are always some that have mutated,
or worse, exchanged genes with other flu viruses: a bit of bird flu, a bit
of swine, maybe a gene from a bat flu virus. No human immune system
would have seen such new viruses, and so, settling deep into a lung of
the first humans they encounter, they are free to infect lung cells and
reproduce. The immune system responds, sending cells called
neutrophils and macrophages into the air sacs of the lungs where they
accumulate and make breathing difficult, but do not control the
infection well. Fever, chills and muscle ache result. Then we cough
millions of new viruses over to other lungs.
If the changes in a virus are small, then the immune system rallies. The
naïve immune system takes a week or two to produce antibodies
specific for a new virus. If a similar virus has previously infected a
patient, the response may be faster. If the change in the virus is major
and the human immune system fails to recognize it at all, then the virus
can spread around the world and cause a pandemic. There were
catastrophic pandemics in 1918, 1968, 1977 and 2009-2010. The 1918-
1919 epidemic was caused by an H1N1 virus and killed many young
people, including soldiers. One speculation is that people who were
older in 1918 had been exposed to a mild H1N1 virus in the late 19th
century and were protected. Everyone else was born too late.
Usually the elderly are more vulnerable to flu because immune systems
decline with age. For years, I taught histology, the study of tissues, to
first-year medical students and we would look at stained tissue slices of
the thymus from a young person and from senior citizens. Under the
microscope, the young thyroid was a thing of order and beauty. The
seventy ear old thyroid looked like a shipwreck, although it still more or
less worked, providing essential T immune cells to the body.
Thousands of flu related deaths occur in nursing homes every winter,
which is why Sanofi-Pasteur, a French vaccine maker, produces a
fortified vaccine for people over 65. One large study that I read
indicated that the fortified vaccine was 30% more effective than the
standard vaccine in reducing flu cases. These large clinical trials are
difficult and I am not completely convinced, but I got the fortified
vaccine anyway.
Viruses that cause measles, mumps, polio, chickenpox or other diseases
don’t vary; their genomes are relatively stable, making them sitting
ducks for our vaccines. Influenza, being unpredictable, requires a
vaccination every year. But could that change? Could influenza become
like measles and other infections that require less frequent
inoculations?
In 2011 I wrote a column titled “The Flu Again but Maybe Not Forever”,
which suggested that a vaccine could control all variants of the influenza
virus. I recently read a 2018 review that explained all of the
approaches that have been taken since then. Most of them take
advantage of the fact that the Hemaglutinin protein varies among
strains, but it is a big molecule, and certain parts of it do not vary. The
studies provoked the immune system with the unchanging bits of
Hemaglutinin and that seems to protect against multiple viruses. So far
there have been 14 human clinical trials all over the world and there
seems to be protection. When do we replace the semi-reliable yearly
injections with a new and relatively untested new vaccine? Not yet, I
think, but stay tuned.
Richard Kessin is Professor Emeritus of Pathology and Cell Biology at the Columbia
University Medical Center. He lives in Norfolk and can be reached at
Richard.Kessin@gmail.com.