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 other diseases.”
“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 spotted first in China in November 2002. The virus sickened 8,096 and killed 774 worldwide by July 2003, according to the World Health Organization (WHO). SARS was brought under control with classic public health techniques: epidemiological investigations, patient isolations, quarantines of exposed people and stringent restrictions on travel.
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.
“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, or visit the Vaccine Research Center web site http://www.niaid.nih.gov/vrc/clintrials/clinstudies.htm.
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 to WHO.
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
News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Researchers have used the SARS coronavirus (top image shows virus cross-section with DNA inside viral envelope) to develop two different types of vaccines that are now in human clinical trials.
Chinese researchers have developed a vaccine based on an inactivated SARS virus (lower left). This stylized image shows a shrunken virus particle with less well-formed spikes to illustrate how the inactivated virus (lower left) differs from the live virus (top). These changes render it unable to infect people. Human clinical trials of the Chinese vaccine began in May 2004.
U.S. researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have developed a DNA-based SARS virus (lower right). The DNA vaccine includes the gene (shown in gold) that encodes the protein that makes up the spikes on the virus’ outer envelope. The SARS virus uses these spikes to gain access to cells it infects. The gene is slightly modified and inserted into a small circular piece of non-SARS virus DNA called a plasmid (shown in purple). In the body, the DNA vaccine coaxes cells to manufacture the SARS spike protein. The immune system should respond by mounting a defense against the spike protein which would protect the person from SARS. NIAID began testing the vaccine in people in December 2004.
NIAID is a component of the National Institutes of Health (NIH), 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.
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