|Experimental Shingles Vaccine Proves Effective in Nationwide Study
Stronger version of chickenpox vaccine cuts incidence and severity of shingles in older adults
In one of the largest adult vaccine clinical trials
ever, researchers have found that an experimental vaccine against
shingles (zoster vaccine) prevented about half of cases of shingles a
painful nerve and skin infection and dramatically reduced
its severity and complications in vaccinated persons who got the
disease. The findings appear in the June 2 issue of The New
England Journal of Medicine.
The Shingles Prevention Study, conducted over 5 ½-years,
was led by the Department of Veterans Affairs (VA) and carried
out in collaboration with the National Institute of Allergy and
Infectious Diseases (NIAID), part of the National Institutes of
Health (NIH), and Merck & Co., Inc. (Whitehouse Station, NJ).
“This is very promising news for older persons,” says Stephen
E. Straus, M.D., an infectious diseases specialist at NIAID and
Director of the NIH National Center for Complementary and Alternative
Medicine, who participated in the design, oversight and conduct
of the trial. “These striking results indicate for the first
time that we can use a vaccine to prevent shingles, one of the
most common and debilitating illnesses of aging. And among vaccine
recipients who did get shingles, the episodes generally were far
milder than they otherwise would have been.”
“For some people, shingles can result in months or even years of
misery,” comments study leader Michael N. Oxman, M.D., an
infectious disease specialist at the San Diego VA Healthcare System
and the University of California, San Diego.
Shingles, also known as herpes zoster, is caused by reactivation
of the virus that causes chickenpox. Once chickenpox infection
has run its course, the virus is not eliminated; rather, it retreats
to clusters of sensory nerve cells usually located near the spinal
cord, where the virus persists in a dormant state. As immunity
weakens with advancing age, the virus can reactivate, multiply
in and damage sensory nerve cells to cause pain. It then migrates
to the skin, causing the blistering rash of shingles.
Generally, shingles first manifests as pain, itching or tingling
in an area of skin on one side of the body or face. Then a painful
blistering rash develops in that same area of skin; the rash can
take two to four weeks to heal.
Anyone who has had chickenpox which includes most adults
in the United States could develop shingles, though not all
will. The two major risk factors are increasing age and declining
immunity. Half of all people who live to age 85 will get the disease.
Experts estimate more than a million new cases of shingles occur
in the United States each year.
The trial was conducted at 22 study sites nationwide, including
16 VA medical centers and six clinical research sites outside the
VA system coordinated through NIAID. Between November 1998 and
September 2001, the multicenter research team enrolled more than
38,500 men and women age 60 or older into the study. Half of the
participants received a single injection of the zoster vaccine a
live, weakened form of varicella-zoster virus, the virus responsible
for chickenpox; the other half received a placebo vaccine. Neither
the researchers nor the participants knew who received vaccine
and who received placebo until after the study was over. The zoster
vaccine used in the study, manufactured by Merck, is a new, more
potent version of the chickenpox vaccine used to prevent chickenpox
in millions of American children every year since 1995. The zoster
vaccine was developed specifically for study in older adults.
During an average of more than three years of follow-up, the vaccine
reduced the incidence of shingles by 51 percent: 642 cases of shingles
occurred among those in the placebo group compared with only 315
in the vaccinated group. Among all vaccine recipients, the total
burden of pain and discomfort due to shingles was 61 percent lower
than in placebo recipients. Moreover, the zoster vaccine reduced
the incidence of postherpetic neuralgia (PHN) a form of chronic
nerve pain that is the most common serious complication of shingles by
two-thirds compared with placebo. The vaccine was well tolerated,
with the rates of serious adverse events low and local reactions
at the vaccination site generally mild.
“As people live longer, and the proportion of older people in our
population increases, it is highly likely that the prevalence of
shingles will increase. A preventive shingles vaccine would be
an enormous boon for the health and quality of life of seniors,” says
Anthony S. Fauci, M.D., NIAID director. “We are extremely
gratified that this public-private partnership has led to these
exciting results, which have the potential to greatly benefit seniors
in years to come.”
Approximately 12 percent of older people with shingles experience
pain lasting for 3 months or longer (the definition of PHN used
in the study). As people age, however, shingles-associated nerve
pain increases in frequency and severity. This complication may
occur in nearly one-third of persons with shingles who are 60 years
of age or older.
Patients with PHN often describe the pain as burning, throbbing,
aching, stabbing or shooting, and it can cause both physical and
emotional suffering. What can be most distressing and debilitating,
according to these patients, is that at least 90 percent of them
have allodynia pain caused by something that ordinarily is
not painful, such as clothing touching the skin, or a cool breeze.
Simply dressing and having a shirt touch the side of the body that
is affected can be excruciating.
Postherpetic neuralgia is difficult to treat. Antiviral medications
can speed the healing of shingles and reduce the severity of nerve
damage caused by the disease, but only if these medications are
used within 72 hours of the first sign of a shingles rash. Thus,
it is important for people to recognize the symptoms of shingles
and get to a doctor quickly. Antiviral medications do not help
relieve PHN once it has begun.
The researchers emphasize that the zoster vaccine was tested only
as a preventive therapy and is not intended as a treatment for
those who already have shingles or postherpetic neuralgia. On April
25, Merck announced that it had submitted a license application
to the Food and Drug Administration for the zoster vaccine. If
approved for use, the research team estimates the vaccine could
prevent 250,000 cases of shingles that occur in the United States
each year and significantly reduce the severity of the disease
in another 250,000 cases annually.
The study was funded by the VA and by Merck, which supplied the
vaccine and placebo. The James R. and Jesse V. Scott Fund for Shingles
Research provided additional funds.
NIAID is a component of the National Institutes of Health, an agency
of the U.S. Department of Health and Human Services. NIAID supports
basic and applied research to prevent, diagnose and treat infectious
diseases such as HIV/AIDS and other sexually transmitted infections,
influenza, tuberculosis, malaria and illness from potential agents
of bioterrorism. NIAID also supports research on transplantation
and immune-related illnesses, including autoimmune disorders, asthma
Additional media contacts:
Department of Veterans Affairs: Jim Blue
VA National Story Program
Merck & Co., Inc.: Christine Fanelle
Merck Vaccine Division
News releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at http://www.niaid.nih.gov.
Reference: MN Oxman et al. A vaccine to prevent herpes
zoster and postherpetic neuralgia in older adults. The New England
Journal of Medicine 352(22):2271-84 (2005).