NIH awards $9 million grant to study aging and immunity to infections

The Trudeau Institute today announced that faculty member Laura Haynes, Ph.D., was awarded a grant from the National Institutes of Health (NIH) to study how aging impacts the immune system's response to influenza infection and vaccination. Entitled "Aging and Immunity to Infections," the award is one of the largest program grants funded this year by the NIH's National Institute on Aging, amounting to more than $9 million over a five-year period. The grant further funds Dr. Haynes' breakthrough study regarding age-related decline in immune functionality that was just released online in the scientific journal Aging Cell.

“This is a great investment for the Trudeau Institute and for the North Country”

Infectious diseases, such as influenza, lead to increased disease and mortality in the elderly. Annually in the United States, influenza causes 200,000 hospitalizations and 36,000 deaths, 90 percent of which occur in older adults. Additionally, the elderly are more vulnerable to infection because vaccine efficacy is significantly reduced in older populations. While it is well known that the adaptive immune response to influenza infection and immunization declines with aging, the Haynes laboratory's recent studies found that there are additional changes in the immune system that had not been previously appreciated. These newly discovered changes contribute significantly to the age-related decline in immune function.

Earlier research from Dr. Haynes' lab has shown that there are age-related declines in the function of immune cells that respond to vaccination. Specifically, immune cells from aged individuals show slower and reduced overall functional responses when compared with cells from younger individuals. They also successfully demonstrated that these changes are intrinsic to the immune cells themselves. That is, even if aged cells are transferred into young hosts, they still exhibit reduced function.

Breakthrough Research in the Immune Response in the Elderly Leads to NIH Grant

Dr. Haynes' recent investigation of the factors responsible for the decline in immune response to vaccination in elderly patients has led to a major breakthrough. Their study, led by postdoctoral fellow Julie Lefebvre, was published online on June 11, 2012 in the scientific journal Aging Cell. The study demonstrates that, in addition to intrinsic defects in aged immune cells, there are changes in the aged environment, including secondary lymphoid tissues such as the spleen and lymph nodes. These changes are the result of disorganized expression of molecules that direct immune cell movement. The result is that immune cells in aged individuals are not directed properly, and their response is slower as a result.

This revelation helps explain how aging impacts the immune system and the mechanisms involved. Only when the specific defects are determined can strategies be developed to overcome these defects and develop more effective vaccines for the elderly.

Importantly, this study also demonstrates that one of the main factors responsible for this delay is an age-related change in the molecules that direct the movement of immune cells. Small molecules in the immune system, known as chemokines, are responsible for the proper movement of immune cells during a response to vaccination or infection. Proper movement of the cells is essential for a robust immune response since many immune system cells function via direct cell-to-cell contact with each other. Without this contact, the immune response is much less effective. This is the first time this kind of mechanism has been appreciated in aged individuals.

Future Research Focuses on How Aging Impacts Response to Flu and Infection

With the support of the $9 million multi-year grant from the NIH, the Trudeau research will focus on how aging impacts the immune response to influenza infection and vaccination and then importantly move this research to human trials.

"This is a great investment for the Trudeau Institute and for the North Country," U.S. Senator Kirsten E. Gillibrand said. "Trudeau is home to some of the world's brightest minds and cutting-edge innovation. When we invest in new ground-breaking research, we can unlock treatments to some of humanity's oldest and deadliest diseases - improving lives and saving lives."

The goal of Dr. Haynes' five-year program is to define how aging impairs immunity and to identify vaccination strategies that will overcome the impairments. As the research develops, colleagues at the University of Massachusetts Medical School and the University of Connecticut Health Science Center will test the discoveries of influenza vaccines in elderly mice and their translation to the elderly in human trials.

According to Dr. Haynes, "This program is vitally important for moving the field forward towards development of new vaccine strategies for the elderly. Our basic research findings in animal models will be confirmed in human studies at the collaborating medical centers. We expect to have new influenza vaccine candidates by the end of this translational research project."