4:00 Dose of Fluology: Shifting, Drifting, VaxnTamiFlu Escaping...

Shifting, Drifting, VaxAndTamiFlu Escaping...

A good deal of this series has talked about novel/pandemic flu strains, and how they arise.  The process of new strain development detailed at 3:00 is called antigenic shift, and it occurs very suddenly and more or less "completely".  One changing event generates a new strain.  We also talked (albeit indirectly) about how these strains will not be covered by flu vaccines, since they are designed using existing flu strains.  This begs a question:

If there is a certain amount of flu vaccine failure each year, and there is not a new pandemic strain every year, how can that happen? 

This happens because of the sneaky and subtle cousin of antigenic shift, antigenic drift.  Influenza has a design "flaw" of sorts, in that it is not particularly good at making exact copies of itself.  Think of a hand-copied note vs. a scanned image.  The scanned image is nearly always going to be perfect no matter how many times the file is copied, whereas the handwritten note?  Not so much.  I put "flaw" in quotes because it isn't really a flaw at all.  Influenza benefits tremendously from this variation.  It allows the virus to escape the immune system of previously infected people so that they can be re-infected.  By the same logic, if it has changed (or, "drifted") enough from the original version, it can infect vaccinated people.  This is what leads to vaccine failures: the person has raised an immune response, but the circulating viruses have escaped it by antigenic drift.  This happens variably by year.  Some years it does not happen much, and the flu vaccine works very well.  Other years it happens to a substantial extent-we call those "bad match" years.  In the same way that immune responses (naturally derived or vaccine-associated) are escaped, TamiFlu and Relenza can also be escaped.  The "N spike" drifts just as much as the other components, and if it drifts enough, the medications stop binding to it.  When that happens, they no longer work.

Antigenic shift may be more dramatic, but antigenic drift is just as important to influenza pathogenesis.  In fact, I'd argue it's more important.