Flu Shot

The nurse's warning startled Deem: shouldn't the effects of a flu vaccination last for years, he wondered, the way vaccinations for polio or smallpox do? He decided to look into what other researchers had found out about the immune system and how it works. The nurse, he discovered, had been right: the risk she mentioned is due to a biological phenomenon known as “original antigenic sin”, first discovered in people and farm animals in 1953.

The term is a nod to both science and theology. An antigen is biologists’ term for an invading organism, such as the influenza virus. Original sin is a theological concept that accounts for human flaws. Original antigenic sin describes an apparent failing in the human immune system: it may recognize a certain strain of a disease, such as this year’s strain of flu virus, but then tries to combat an entirely different strain by "remembering" how it fought the first strain it encountered. As a result, if you skip a flu shot one year, Deem says, you may be more likely to get the flu during that year, compared to your chances of illness if you had never gotten a flu shot in previous years. "It’s as if the immune system didn't have any memory whatsoever, and simply started to learn about this year's flu from scratch," Deem says.

Three antibody fragments bind to the protein surface of influenza virus. image: Protein Data Bank, Rutgers University

Next time you are exposed to that particular antigen, you have antibodies that usually protect you. But viruses that mutate as quickly as influenza does, may have several different areas where antibodies could latch on—areas that may change every year, foiling existing antibodies.

"The flu changes from year to year because of random mutations," says Deem. "When someone gets the flu, lymph nodes under the arms and under the cheeks swell because they're producing different antibodies. Those antibodies become better and better at recognizing the flu. Those antibodies are still around the next year, and sometimes those antibodies don't respond as well to a new flu as new antibodies would. So the immune system’s memory actually inhibits the system from learning something new about the flu next year."

At Rice, Deem and his research team developed a computational model that demonstrates how original antigenic sin operates. "Our interest was in understanding this phenomenon of original antigenic sin in a quantitative way," Deem explains.

At present, to help combat new flu strains, every flu vaccine contains three strains, and one strain is changed annually. Deem hopes that with his model, “perhaps we could point towards better design efforts for changing the flu vaccine from year to year."

His research also could contribute to the development of vaccines for other viral diseases to which original antigenic sin applies as well—HIV, chlamydia, hepatitis, and dengue fever. Deem points out that their common feature is either multiple strains, as in dengue fever, or very rapid mutation, as in HIV and the flu.

Meanwhile, he recommends a flu shot every fall: "The flu shot protects you quite a bit against the flu this year, and your increased susceptibility next year from original antigenic sin is much smaller than the increased protection this year. And if you get the flu shot next year, you’ll be protected against next year's flu.” Anyone who is particularly susceptible should not skip an annual flu shot.

Deem's research appeared in the August 8, 2003 issue of the journal Physical Review Letters and was presented on September 8, 2003 at the national meeting of the American Chemical Society. It was funded by the National Science Foundation (NSF), and the Camille and Henry Dreyfus Foundation, Inc.