Despite millions of needle jabs to bolster flu immunity each year, the efficient influenza virus continues to evolve to get around these biological blockades by altering its surface proteins. As people in a population become immune to the virus through vaccination or exposure, however, they change how the virus mutates and, ultimately, the chances of a larger outbreak.

But precisely how do small changes in the virus and a group's immunity impact the risk of an influenza epidemic?

Because human populations have a wide history and variable rate of immunization, researchers have had a difficult time predicting how an influenza strain will change in response to a vaccinated population. "We do not know how changes in viral [surface proteins] translate into immune escape," wrote the authors of a new paper on the topic. So to study the question, researchers turned instead to ponies.

Like people, some horses have been being vaccinated against the flu (H3N8 in their case, H3N2 in ours) for decades. And, as the equine flu has many similar characteristics to seasonal influenza A, groups of ponies provided a useful controlled experiment to track the virus behavior. 

One group of ponies received vaccination against a common flu strain while another did not. By analyzing the data both the microscopic level (the molecular changes in the flu virus) and the macroscopic level (the infection patterns in the herds), the researchers were able to track the dynamics of the illness's spread. The results were published online Thursday in Science.

A virus with just two or more key differences in amino acids on its surface protein hemagglutinin (the "H" in formal flu designations) made the ponies more susceptible. And once the virus had changed enough to appear novel to the body's immune system, larger outbreaks were more likely.

The researchers also found that even if pandemic vaccines are not a perfect match for circulating virus strains, vaccinating a large portion of the population can create enough immunity to slow the spread and even prevent a larger outbreak.

Through further study, "public health officials will be able to assess the usefulness of a vaccine based upon its relationship to the current influenza strain and the population's immunity level," Andrew Park, an assistant professor at the University of Georgia's Odum School of Ecology and College of Veterinary Medicine and lead study author, said in a prepared statement. 

Honing in on the characteristics of flu mutations and outbreaks is not only important for the current H1N1 pandemic, but also for the annual seasonal flu, which kills an average of about 36,000 people in the U.S. each year. As the authors note, even the H3N2 strain mutates enough during the course of every two to five years that the new iterations may not longer be recognizable to a previously exposed immune system. 

Beyond fighting the flu, findings could also help to combat "a broad class of infections, including emerging, reemerging and extant infectious disease," the paper authors wrote.

Image of ponies from the study courtesy of Science/AAAS