First U.S. SARS Vaccine Trial Opens at NIH
Powerful research tools that speed up vaccine development have
led to the start today of human tests for a preventive vaccine against
the respiratory disease SARS. The disease killed hundreds of people
around the world before it was brought under control in 2003 with
aggressive conventional public health measures.
Researchers at the Vaccine Research Center, National Institute of
Allergy and Infectious Diseases (NIAID), part of the National Institutes
of Health (NIH), will conduct the trials. The experimental vaccine
against SARS, or severe acute respiratory syndrome, will be tested
on 10 healthy volunteers at the NIH Clinical Center in Bethesda,
MD. The clinic will do periodic follow-up exams on each volunteer
for 32 weeks.
"This experimental vaccine is an outstanding achievement by
NIAID researchers," said Health and Human Services Secretary
Tommy G. Thompson. "It is a model for research that could greatly
shorten the time needed to create vaccines to be tested against
"The Vaccine Research Center, a cutting-edge facility established
here at NIH just five years ago, encompasses the entire spectrum
of vaccine development from basic research to clinical testing,"
says NIH Director Elias A. Zerhouni, M.D. "This is why our
team at NIAID has been able to develop this vaccine at an unprecedented
pace, using technological discoveries that were not available just
a few short years ago."
The primary goal of the study is to determine if the experimental
vaccine is safe in people. A secondary goal is to assess how well
the vaccine stimulates the immune system to produce antibodies and
cellular immunity, in this case, focusing on the SARS spike protein.
The spike protein protrudes from the virus' outer envelope and helps
it bind to cells it infects.
SARS was brought under control with classic public health techniques:
epidemiological investigations, patient isolations, quarantines
of exposed people and stringent restrictions on travel. SARS was
spotted first in China in November 2002. The virus sickened 8,096
and killed 774 worldwide by July 2003, according to the World Health
The sudden appearance of SARS, its severity, and its ability to
be spread far and fast by international travelers, spurred medical
researchers. NIAID researchers developed the vaccine with unprecedented
speed. Just 21 months passed from when international health officials
recognized SARS as a new infectious disease to the opening of the
NIAID human clinical vaccine trial. It often takes decades for scientists
to develop a successful vaccine against an infectious disease.
"In the case of SARS, we have dramatically cut vaccine development
time with powerful new tools from two different fields, molecular
biology and information technology," says Anthony S. Fauci,
M.D., director of NIAID.
Instead of using weakened or inactivated virus, which is typical
for vaccine development, the new vaccine is composed of a small
circular piece of DNA that encodes the viral spike protein. Scientists
modified the DNA to minimize the risk of it combining with the SARS
virus or other viruses of the SARS type, called coronaviruses.
Scientists expect that the DNA will direct human cells to produce
proteins very similar to the SARS spike protein. The immune system
should recognize these proteins as foreign and then mount a defense
against them. If the vaccinated person ever encounters the actual
SARS virus, his or her immune system will be primed to neutralize
"It is truly remarkable that less than two years ago we were
facing an unknown global health threat, and now we are testing a
promising vaccine that may help us to counter that threat should
it re-emerge," Dr. Fauci said.
After SARS was identified as a disease, researchers worked hastily
to identify the cause of the mysterious respiratory ailment and
to develop therapies and vaccines. By April 2003, NIAID-funded researchers
in Hong Kong were the first to show that SARS is a viral disease.
They soon proved that a newly emerging coronavirus causes SARS.
By May, an international collaboration of researchers had decoded
the genetic sequence of the SARS coronavirus, opening many avenues
of research to develop diagnostic tests, therapies and vaccines.
An NIAID team, lead by NIAID Vaccine Research Center Director Gary
J. Nabel, M.D., used the available SARS coronavirus genomic information
to develop a vaccine based on the gene for the SARS spike protein.
The vaccine performed very well in mice, reducing the levels of
virus in the lungs of infected mice by more than a million-fold,
Dr. Nabel and colleagues reported in Nature in March 2004.
"Two years ago, we didn't know that this virus existed. Today,
we begin clinical trials of a promising vaccine candidate. We owe
the speed of this research to modern molecular genetics. The technology
enables us rapidly to translate scientific discoveries into clinical
interventions and improves our ability to battle these ever-evolving,
highly lethal microbes," says Dr. Nabel.
Under a contract with NIAID, Vical Inc. of San Diego, CA, is producing
the SARS vaccine for the NIAID clinical trial. For more information
on the SARS vaccine trial, phone the Vaccine Research Center's toll
free number 1-866 833-LIFE.
Chinese researchers began human testing of a SARS vaccine in May
of this year. The Chinese vaccine trial uses an inactivated SARS
virus vaccine developed through conventional vaccine technology.
While the bulk of SARS cases were in China, Hong Kong and Singapore,
eventually cases also occurred in Canada, Europe and the United
States, according to WHO. There were 27 probable SARS cases in the
United States. No U.S. residents died of the disease, according
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.
Reference: Z Yang et al. A DNA vaccine induces SARS coronavirus neutralization and
protective immunity in mice. Nature 428:561-4 (2004). DOI: 10.1038/nature02463