"I want to point you to new research," observed cellular immunologist Susan Swain at the Trudeaux Institute in Saranac Lake, N.Y.
"The younger you are when you're vaccinated against influenza, the better and longer you're protected from the disease. Because immune system function declines with age, the elderly are more susceptible to infection and are therefore prime candidates for vaccination. However, paradoxically, the ability of the immune system to respond vigorously to vaccination is also impaired with age. Therefore, vaccination is most beneficial if it takes place at an early age."
Can it succeed both ways?
Annual shots against the flu are a ritual protecting the elderly and the children. How about vaccination against forgetting, as advancing old age bedevils the waning of memory? Researchers staffing the Trudeaux Institute took up this challenge. The result of their efforts is a paper dated Dec. 9, 2003, in the Proceedings of the National Academy of Sciences (PNAS) titled "CD4 T cell memory derived from young na ve cells functions well into old age, but memory generated from aged na ve cells functions poorly."
Swain, the institute's president and director, is the article's senior author. "As we become aged," she explained, "CD4 T cells ready to respond to antigens and pathogens both become defective. They don't respond very well and are not able to give rise to very good memory. This may account for the difficulties of vaccination as people age. Hence, there is a good reason to vaccinate people during their middle years, so immune system na ve cells may turn into memory cells. And their immunity may be very durable. If it is generated in young and middle age, it lasts for a very long time."
Vaccinating Kids, Grown-Ups In Ideal Age Brackets
"The newsworthiness of our hypothesis," Swain continued, "is that we vaccinate children, which certainly does the work for them. And for immunizing against infections like the flu, that's likely to work if recipient adults encounter infectious pathogens. We should consider vaccinating them earlier in their life.
"Another aspect in the elderly is using strategies that will overcome immune system defects. It's one of the things we're studying currently. One is trying to figure out what the defect is and devise corrective remedies.
"To carry out that strategy, we turned to certain adjuvants in vaccines that make them more resemble live target organisms. Adjuvants increase the response, even if the aged na ve cells are otherwise defective. Our hope is certainly there to do some vaccinations with adjuvants for human patients. At the moment," Swain said, "the only adjuvant approved in human use is alum - aluminum potassium sulfate. In medical practice, alum is used as astringents and styptics. It's not very effective, but a number of companies are exploring adjuvants with even better antibodies. They are contending with pathogens - mainly bacteria or viruses. Many of the vaccines don't have these components but aren't attenuated. It's important for us to determine which adjuvant components are most effective for which kind of vaccine, and then add them back to fabricate a new, more effective vaccine.
"CD4 T cells are one of two major types of T lymphocytes. They are the cells that are defective in AIDS infection. You get very poor immune responses," Swain went on, "if you don't have CD4 T cells to induce T cells without CD4 T cells to make antibodies. An effective antibody could gain access to B cells, which have more ability to develop other types of immunity as well. The T-cell name, by the way, was derived from the thymus gland - which accounts for T' lymphocytes."
Turning Lymphocytes Into Memory Cells
"We did two kinds of experiments in mice," Swain recounted. "Our research involved introducing antigens into young mice (2 to 4 months old) and aged mice (14 to 16 months), then observing their ability, even a year later, to respond when the antigen was re-introduced. In one instance, we took na ve immune cells out of aged mice. We stimulated their cells outside of the animal because we first wanted to study their na ve cells. We just added some components needed to induce an immune response. Those are the clutters of things we have described over the past decade or so. What we did in addition to this was develop in a tissue culture dish a population of effector cells that have all the immune functions we expected would occur. Then we could re-introduce them back into the animals, where they became memory cells.
"After we took the cells from aged mice," Swain went on, "when we looked later, the memory cells didn't function very well. So that was the first half of our transgenic mice experiment. The second half was to make effectors from young cells, put them back into the same animals, and let them age for a period of time. They turned out to be perfectly capable of functioning."
Swain and her co-authors have just received a $1.78 million grant from the NIH's National Institute of Aging. Its focus is additional research on the impact of aging on CD4 and CD8 responses to viruses. The grant, for a five-year period through June 2008, could generate important information aimed at elucidating immune defects that arise in cells from aged individuals. Hence, it could contribute to further development of strategies to effectively vaccinate the elderly.
Swain's paper summed up its findings: "Because the elderly exhibit a greater susceptibility to infectious diseases such as influenza, they are often prime candidates for vaccinations. However, evidence is now increasing that the efficacy of these vaccinations in the elderly is greatly reduced compared with young populations. Memory generated by using na ve T cells from young mice responds well, even after one year of priming. In contrast, memory generated during old age is defective both in vitro and in vivo." It concluded by suggesting that "na ve CD4 T cells from aged mice exhibit a heritable defect."