For Seniors, Vaccines Often Miss Their Mark

Vaccines don't work as well in the elderly as in the young, leaving many of the sickest people vulnerable to disease. But immunologists are learning why immunity falters and might soon be able to give shots more punch.

This fall, millions of seniors will troop to a clinic or doctor's office for a flu shot. But for people over 65, a sore arm doesn't guarantee a flu-free winter. Up to 70% of them won't develop immunity to this year's bug, versus about 10% of young adults who receive the shot. Other vaccines also fail more often in the elderly. The immune system sags with age, and it drags down vaccine responsiveness, creating a Catch-22 for seniors. Because their immune defenses weaken over time, they need the protection that shots confer more than ever. But they can't muster the proper resistance because of their weakened immune system.

The need to improve vaccine performance in the elderly grows every year as the population gets older. But researchers have only recently started probing how shots work--or fail--in the elderly, says immunologist Rita Effros of the University of California, Los Angeles. Most vaccines are "developed in young, healthy animals and tested on young, healthy people," she says.

Nevertheless, she and other researchers are bullish that recent discoveries might eventually help liberate the elderly from their cruel bind. Scientists are beginning to understand the changes that stifle older people's response to vaccines. And some investigators are delving into possible solutions, which range from beefing up current immunizations to rejuvenating the graying immune system. Until such remedies are ready for the clinic, seniors might benefit from some simple changes to their health care. For example, shifting the schedule of recommended vaccinations might help the elderly stay healthy longer.

A vaccine dupes the body's defenses into responding as if a full-scale bacterial or viral onslaught were under way. During an infection, the immune system pumps out combat-ready T and B cells, some of which linger after the battle as memory cells. These guardians can remain on duty for the rest of a person's life, screening the body for invading pathogens. A vaccine triggers the same response. Then, if the microbe a vaccine targets ever appears, these prefab defense cells divide swiftly to produce an army to attack the interloper.

To mount a hearty response to this year's flu vaccine, a person needs a supply of fresh T cells. However, the source of these cells dries up--literally--with age. T cells are born in the bone marrow, but they mature and learn their chops in the thymus, a spongy gland nestled behind the breastbone. As we get older, the thymus, which can be nearly the size of the heart in a newborn, withers and fills with fat. By age 60, it's virtually gone. Losing this gland undermines the immune system's response to vaccines because without it, "you are dependent on the T cell pool generated while you are young," says immunologist Beatrix Grubeck-Loebenstein of the Institute for Biomedical Aging Research in Innsbruck, Austria.

Running low on fresh cells is only one of the immune system's problems. The body usually has plenty of memory T cells left over from previous battles, but these veterans are often duds. Unlike fit, young cells, they can't proliferate rapidly when a microbe appears. Instead of fading away, these old soldiers linger and cause trouble, hampering the body's response to vaccines. Three years ago, for instance, immunologist Cornelia Weyand of Emory University in Atlanta, Georgia, and colleagues gauged immunity in retirement home residents who were vaccinated against flu. The researchers discovered that patients whose immune system ignored the vaccine carried large numbers of the feckless T cells. Scientists are not sure how the sluggish cells interfere with vaccines. They might release chemicals that hinder other immune cells or crowd out their younger, more enthusiastic compatriots.

Chronic infections might drive this decline, say Effros and Grubeck-Loebenstein, causing the immune system's ranks to fill with cells as useless at fighting as Sergeant Schultz on Hogan's Heroes. These cells could be the leftovers from a long-term struggle against certain hard-to-evict viruses such as cytomegalovirus (CMV). After decades of fighting, the hypothesis goes, battle-weary T cells lose the ability to divide and fight. If the idea proves true, preventing CMV infection or getting vaccinated against it could keep the immune system robust into old age. The bad news is that a good vaccine doesn't exist, and almost everyone gets infected by this ubiquitous virus.

Insight into how the immune system fails with age has outpaced work on possible correctives. "We understand some of the problems but not how to solve them," says Effros. However, recent studies suggest that even simple changes to vaccine mixtures might bring large improvements. For example, last year researchers at Hebrew University in Jerusalem and colleagues showed that packing flu vaccine inside tiny fatty capsules could nearly double its effectiveness against certain viral strains. Scientists are also probing the use of different chemical additives that rev up the immune system.

Changing the recommended vaccination schedule might also help prevent illness late in life, says immunologist Garnett Kelsoe of Duke University in Durham, North Carolina. Patients might be better off receiving as many vaccines as possible in their 50s, because immune responses decline precipitously beginning in the 60s. This strategy wouldn't work for flu, however, because the virus's speedy evolution necessitates a new immunization every year.

Some researchers are thinking bigger, trying to devise ways to restore the immune system to youthful fettle. One option, says Weyand, is to rear platoons of na ve T cells in culture, then inject them into seniors to compensate for the loss of the thymus. Other researchers hope to coax the organ to regrow or to convince stem cells to build a fresh thymus. Another possibility is to filter the troublemaking T cells from the blood, using a procedure akin to dialysis for kidney patients, Effros says. None of these ideas is ready for the clinic, and the more than 35 million Americans over age 65 will have to take their chances with the flu vaccine this fall. But within a few years, researchers might be able to ensure that seniors get more from a shot than an aching arm.

Mitch Leslie is a science writer in Albuquerque, New Mexico. He awaits a shot that will prevent gray hair.