One of the greatest medical innovations in our society is something we rarely think about on a daily, weekly or even monthly basis. This innovation has single-handedly changed the course of medicine, completely eradicating certain diseases from our lexicon. This miraculous invention is, of course, the vaccine. As children, we receive vaccines on a very specific schedule to protect us against a host of viral and bacterial diseases. Nearly all of these vaccines only need to be administered once or on a series/booster schedule; however, the only vaccine given on a yearly basis is the influenza vaccine to protect against new strains of the flu virus. So what's so special about the influenza virus?

In a broad sense, the flu virus can escape our immune system by mutating its genetic sequence, essentially cloaking it from our body's detection. The degree of mutation in viruses is dependent on the type of genetic material in the virus. If the virus contains double-stranded DNA, which has an efficient error-checking system, it will be fairly stable from strain to strain, allowing our immune systems to recognize the virus year after year. However, if the virus contains RNA, a single-stranded structure, the frequency of mutations increases exponentially. Unlike DNA replication, RNA replication doesn't have an efficient "spell-check" , making it extremely susceptible to those replication errors that lead to mutation. This explains why a vaccine against varicella (chicken pox), a DNA virus, keeps the immune system prepped for years, whereas a vaccine against influenza, a RNA virus, is not sufficient to  protect the immune system from one year to the next.

The influenza virus can use two methods to escape immune detection, both driven by RNA mutations.

One method is known as antigenic drift. The flu virus has specific receptors that allow it to bind to host cells and enter healthy tissue. Our immune system creates antibodies that bind to these receptors, allowing our "defense" cells to recognize and get rid of the virus. However, subtle mutations in the influenza virus can change the identity of this receptor, making it invisible to previously made antibodies and allowing the flu to continue attacking host cells. Through these various mutations, a new strain of influenza can be created that is different from the original.

Here's an image explaining antigenic drift:

Image courtesy of Janeway Immunobiology

The other method of viral escape is antigenic shift. A single host cell can be infected by two slightly different strains of an influenza virus at the same time. Antigenic shift occurs when the RNA from these different viruses combine to form a new RNA strand that encodes for a completely different receptor. The immune system has no way of recognizing and attacking this new receptor, thus making host cells susceptible to viral attack. Where antigenic drift creates subtle changes in the flu virus, antigenic shift contributes to larger changes in the antigenicity of the virus. As a result, antigenic shift is responsible for the large scale changes associated with widespread virus epidemics when no vaccine exists

Below is an image explaining the process of antigenic shift:

Image courtesy of Janeway Immunobiology

In short, RNA mutations provide the influenza virus with a way to evolve at breakneck speed, allowing it to evade attack from our immune systems. This "micro-evolution" of influenza is the major player in the continual arms race between our immune system and the viral assault of the flu.

It's these unpredictable mutations that make the creation of a suitable vaccine so difficult to find. Despite these challenges, experts have done a remarkably good job at protecting the population from new strains of influenza year after year.