The flu virus infects up to one-fifth of the U.S. population each year and kills thousands of people, many of them elderly. A new study explains why the flu vaccine is less effective at protecting older individuals, the people it is supposed to protect. 

Flu vaccines, which contain proteins found in circulating viral strains, offer protection by eliciting the production of antibodies -- proteins that help the immune system identify pathogens and protect against infectious disease. While vaccination is considered the most effective method for preventing influenza, it is less effective in the elderly. But until now, the molecular mechanisms underlying this decrease in vaccine efficacy were unknown.

To address this question, researchers identified molecular signatures of immunity to flu vaccination using systems biology approaches, which involve the computational and mathematical modeling of complex biological systems. They vaccinated 212 subjects, including 54 elderly individuals, across five influenza vaccine seasons, from 2007 to 2011, and analyzed blood samples to identify molecular pathways associated with protective antibody responses elicited by vaccination. They also analyzed previously published data for 218 additional subjects.

Using this approach, the researchers identified molecular signatures present in blood samples collected a few days after vaccination that predicted with 80% accuracy whether the vaccine would elicit immune protection approximately four weeks later. Within one week of flu vaccination, young individuals showed high levels of antibody-producing B cells, whereas the elderly showed high levels of immune cells called monocytes, which elicit inflammatory responses in the body. These age-related differences predicted impaired vaccine-induced immune responses observed in the elderly three weeks later. 

Even before vaccination, high baseline levels of B cells, in conjunction with low levels of monocytes and related inflammatory molecules, predicted vaccine-induced immune protection four weeks later.

"This supports the concept that inflammatory responses at baseline may be detrimental to the induction of vaccine-induced antibody responses," says Shankar Subramaniam of the University of California, San Diego. "By providing a more complete picture of how the immune system responds to vaccination, our findings may help guide the development of next-generation vaccines that offer long-lasting immunity and better protection of at-risk populations."