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Why you should get a flu shot: Fortune favors the prepared immune system

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 70-year-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 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.