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Stanford Report, July 10, 2002

Childhood vaccine may offer shingles protection

By KRISTA CONGER

Stanford researchers have found that a childhood vaccine given in adulthood can reduce the risk of shingles, an excruciatingly painful disease that strikes the elderly and people with weakened immune systems.

Researchers studied the effects of an inactivated form of the chicken pox vaccine in cancer patients who were especially likely to develop shingles (also called zoster). It appears possible that the vaccination can prevent healthy elderly people from developing the disease and that other vaccines might be a good way to protect transplant recipients against viruses and bacteria.

"We knew that these patients were at very high risk for zoster," said Ann Arvin, MD, chief of pediatric infectious disease at Lucile Packard Children's Hospital. "We thought we could try to benefit those with impaired immune systems, and also demonstrate that vaccination could help protect others who are at risk for shingles."

Arvin, the Lucile Salter Packard Professor of Pediatrics and professor of microbiology and immunology, is the senior author of the study, published in the July 4 issue of the New England Journal of Medicine. Karl Blume, MD, professor of medicine and chief of the division of bone marrow transplantation at Stanford University Medical Center is a co-investigator.

Shingles is triggered by the same virus that causes chicken pox. While most people recover from chicken pox without incident, the virus then bides its time in nerve cells - a nefarious stowaway, waiting decades for a chance to strike again. When the immune system is weakened by age or disease, the virus springs to life, spurring an itchy, burning rash and a legacy of shooting pain that can last for years.

"It's a very disruptive kind of pain," said Arvin, "The skin becomes so sensitive that it can be difficult to sleep and even the lightest clothing or faint breeze becomes painful." Arvin estimates that even for healthy adults the risk of shingles rises each decade after age 60, increasing to one in five for people in their 80s.

Researchers tested the effect of an inactivated version of the chicken pox vaccine on lymphoma patients about to undergo a hematopoietic cell transplant to combat cancer. Because these patient's immune systems are weakened by the disease and its treatment, up to one third of them develop shingles within 12 months of their transplant. Using an inactivated vaccine reduced the chance of adverse side effects in the study subjects.

Arvin and her colleagues found that only 13 percent of the 53 patients who received one dose of the inactivated vaccine within 30 days prior to the transplant, followed by three additional doses after transplant, developed shingles. On the other hand, 30 percent of the 56 participants in the unvaccinated control group got the disease.

The key appears to be the pre-transplant treatment; a previous study by Arvin that tested only post-transplant vaccination showed no protection. This indicates that some immunity must remain even after the patient's immune system is wiped out during the transplant procedure.

"We would suggest from our data that the same pre-transplant vaccination strategy would work to protect these patients against other viruses and bacteria," said Arvin. "The idea that they are so immunocompromised that you can't benefit these patients by vaccination during the early stage of the transplant is incorrect."

Researchers suspect that the protection against shingles is conferred by memory T cells - virus-specific immune cells jump-started by the vaccine to mount an attack during the transplant and subsequent recovery. When they rated the strength of the T cell immune response to the virus at various times during the transplant, they found that patients in both the vaccinated and unvaccinated groups who went on to develop shingles shared especially low levels of immunity. Those whose T cells responded more strongly to the virus were less likely to develop shingles. Vaccination increased the T cell response to the virus with each dose and protected against shingles.

"It's possible that it's not necessary to give people as many doses of the vaccine as we did in this study," says Arvin. "We may be able to use the immune test to decide when a patient is adequately immunized." Such a test could also conceivably be used to identify elderly people who are at particular risk of developing shingles. However, if an ongoing multi-center study conducted by the Veteran's Administration hospitals, including the Palo Alto Veteran's Hospital, shows that this population can be protected by vaccination it might be simpler to just immunize them, points out Arvin. Results from that study are expected within a year.



New vaccine emulates shingles to boost immune system against the virus (6/7/00)

Ann Arvin appointed associate dean of research (2/7/01)