NIAID Begins Clinical Trial of West
Nile Virus Vaccine
A small trial testing the safety of an experimental
vaccine targeting West Nile virus (WNV) opened today
at the National Institutes of Health's (NIH) Clinical
Center in Bethesda, MD. The vaccine, which will be tested
first in 15 healthy adult volunteers, was developed
for human clinical studies by researchers at the National
Institute of Allergy and Infectious Diseases' (NIAID)
Vaccine Research Center (VRC), and Vical Inc., San Diego,
based on an animal vaccine tested at the Centers for
Disease Control and Prevention (CDC). Vical also manufactures
the experimental vaccine.
"Although the prevalence of West Nile virus disease
fluctuates seasonally and regionally, it continues to
pose a serious public health threat, especially to older
adults and people with weakened immune systems," says
Anthony S. Fauci, M.D., director of the NIAID.
WNV, initially isolated in Uganda in 1937, made its
first U.S. appearance in New York City in 1999. The
virus usually is transmitted to humans through the bite
of a mosquito that has been infected after feeding on
an infected bird or animal. The virus also can be spread
through blood transfusions, organ transplants and breastfeeding,
as well as from mother to child during pregnancy. Most
people experience no symptoms or only mild symptoms,
such as fever, headache and body aches; more serious
cases can lead to infections of the brain and nervous
system, such as encephalitis or meningitis. In 2004,
2,470 cases of WNV disease were reported in the United
States, resulting in 88 deaths. Currently, no WNV vaccine
is licensed for use in humans.
The experimental vaccine is composed of a small, circular
piece of DNA — called a DNA plasmid — that contains
genes that code for two key surface proteins of the
West Nile virus. When the vaccine is injected into the
muscle, the inner machinery of the muscle cells "reads" the
DNA and converts it into two WNV proteins. Recognizing
that the proteins are foreign, the muscle cells display
them on their surface to alert the body's immune system
— both helper T cells, which spur the production of
antibodies to block the WNV from gaining entry into
cells, and killer T cells, which kill WNV-infected cells
outright.
"The DNA vaccine's exploitation of both cellular and
antibody immunity offers a potentially potent defense
against West Nile virus," says Barney Graham, M.D.,
Ph.D., chief of the VRC's Clinical Trials Core Laboratory.
Adds Dr. Graham, "In our experience in clinical trials,
DNA vaccines generally cause few side effects, making
them a promising alternative to conventional vaccines."
Although no DNA vaccine has yet been licensed, other
DNA vaccines developed by the VRC against HIV/AIDS,
Ebola and SARS also are being tested in ongoing trials
at NIH.
Fifteen healthy volunteers between the ages of 18 and
50 will receive three injections of the DNA vaccine
into the upper arm: one at the start of the trial, a
second approximately four weeks later, and a third approximately
four weeks after that. To help force the DNA plasmid
into muscle cells, the vaccine will be administered
by a needle-free injector rather than a conventional
needle syringe. Volunteers will be monitored for possible
symptoms or side effects as well as the body's ability
to generate WNV-specific antibodies and T cells. The
vaccine cannot cause West Nile virus infection or disease
because it does not contain infectious material from
the virus. For more information on the WNV vaccine trial,
call the Vaccine Research Center's toll free number
1-866-833-LIFE, or visit the VRC Web site http://www.niaid.nih.gov/vrc/clintrials/clinstudies.htm.
The vaccine in this study builds upon an experimental
vaccine developed by CDC researcher Jeff Chang, D.V.M.,
Ph.D., of Fort Collins, CO, that has been tested successfully
in a variety of animals, including mice, horses, and
American crows.
Two other human WNV vaccines developed with NIAID support
are currently in Phase I clinical trials. Called chimeric
vaccines, these vaccines combine genes of the West Nile
virus with genes of a closely related virus — yellow
fever virus in the case of a vaccine developed by Acambis,
Cambridge, MA, and dengue virus in the case of a vaccine
developed by NIAID intramural researchers.
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 and allergies.
News releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at http://www.niaid.nih.gov. |