FASTER, PLEASE: Search begins for universal influenza vaccine.

The smallpox vaccine was the first to use the “empirical paradigm” of vaccinology – the same strategy we largely use today. It relies on a trial-and-error approach to mimic the immunity induced by natural infection.

In other words, vaccine developers believe the body will mount an antibody response to something in the inoculation. But they don’t focus on which specific patch of the virus is causing an immune response. It doesn’t really matter if it’s a reaction to a small patch of HA that many strains share, for instance. When using an entire virus as starting material, it’s possible to get many different antibodies recognizing many different parts of the virus used in the vaccine.

The seasonal flu shot generally fits into this empirical approach. Each year, epidemiologists forecast which flu strains are most likely to infect populations, typically settling on three or four. Researchers then attenuate or inactivate these strains so they can act as the mimics in that year’s influenza vaccine without giving recipients the full-blown flu. The hope is that an individual’s immune system will respond to the vaccine by creating antibodies that target these strains; then when he or she comes into contact with the flu, the antibodies will be waiting to neutralize those strains.

But there’s a different way to design a vaccine. It’s called rational design and represents a potentially game-changing paradigm shift in vaccinology.

The goal is to design some molecule – or “immunogen” – that can cause effective antibodies to be produced without requiring exposure to the virus. Relative to current vaccines, the engineered immunogen may even allow for more specific responses, meaning the immune response targets particular parts of the virus, and greater breadth, meaning it could target multiple strains or even related viruses.

This season’s bug moved so quickly that it hit me and one of my sons before we could get in for our already scheduled flu shots.