Dec. 8, 2003 PITTSBURGH, Dec. 4 -- Research by scientists at the University of Pittsburgh School of Medicine and the Graduate School of Public Health (GSPH) in collaboration with colleagues at the Centers for Disease Control and Prevention (CDC) in Atlanta has shown that an adenoviral-based vaccine can induce SARS-coronavirus (SARS-CoV)-specific T-cell and virus-neutralizing antibody responses.
The study, which represents the first published work on the development of a SARS vaccine and comes only a few months after the SARS coronavirus was identified and its genome was sequenced, is reported in a fast track research letter in the Dec. 6 issue of The Lancet.
"It is our hope that this research will lead to a protective vaccine against SARS," stated project leader Andrea Gambotto, M.D., from the departments of surgery and medicine, division of infectious diseases and the Molecular Medicine Institute (MMI) at the University of Pittsburgh School of Medicine.
In the study, researchers immunized six rhesus macaques intramuscularly with a combination of three SARS-CoV vectors. Two additional macaques were immunized with the same amount of empty adenoviral vector and served as controls. After 28 days, the animals received a second vaccination. Six weeks after vaccination, T-cells and antibodies against SARS were detected in all six of the immunized animals, but not in either of the control animals. The intensity of the response varied among animals but was generally largest after the booster vaccination, according to the Pittsburgh researchers. Serum samples from the vaccinated animals, but not from the controls, showed strong neutralizing capacity against SARS-CoV.
"From a scientific perspective, several points are important. We obtained the recombinant vaccine by engineering a common cold virus to express the SARS coronavirus antigens. This is a successful strategy that we are exploring for other infectious diseases such as HIV," said Dr. Gambotto. "After injection, the vaccine acts as a Trojan Horse, first by infecting cells in the body, and then stimulating an immune reaction to the delivered SARS antigens, ultimately conferring protection against the disease. Also, the induced immune reaction appears to be broad: both antibody and cell-mediated immune responses, equally important for protection from viral infections, were detected in the test animals," he said.
Dr. Gambotto went on to say that the researchers will now test the vaccine in ferrets, which have been shown by a group of Dutch researchers to develop SARS symptoms after SARS-coronavirus infection, unlike the monkeys in the current vaccine study.
"This testing is important to fully assess the ability of our recombinant vaccine to protect from subsequent exposure to the SARS coronavirus. We also are soon planning human clinical trials in the near future here at the University of Pittsburgh as part of the MMI initiative," Dr. Gambotto said. The MMI is the nucleus for gene and protein therapy research at the University of Pittsburgh and provides the infrastructure and resources necessary to rapidly translate gene therapy protocols from bench to bedside.
SARS emerged as a threatening and deadly infectious disease last year in China. For Wentao Gao, M.D., Ph.D., research instructor in the department of surgery and co-author of the study, his participation in this research was especially meaningful because SARS claimed several lives in his hometown of Changchun, Jilin. "I am proud of what I have contributed in the development of a SARS vaccine, given that the adenoviral-based vaccine is economical and suitable for a large population. I hope we will soon be able to translate this vaccine into clinical trials to test its toxicity and efficacy," he said.
Other University of Pittsburgh researchers who participated in this study include Leonardo D'Aiuto, Ph.D., and Edward Nwanegbo, M.D., post-doctoral fellows in the department of surgery who work in Dr. Gambotto's lab; Paul D. Robbins, Ph.D., professor of molecular genetics and biochemistry; Simon Barratt-Boyes, Ph.D., assistant professor in the department of infectious disease and microbiology at the University of Pittsburgh Graduate School of Public Health; and Adam Soloff, B.S., a GSPH student who works in Dr. Barratt-Boyes' lab. Additional collaborators are William J. Bellini, Ph.D., and Azaibi Tamin, Ph.D., from the National Center for Infectious Diseases, at the CDC in Atlanta.
The study was funded by a grant from the National Heart, Lung and Blood Institute's Program of Excellence in Gene Therapy. The University of Pittsburgh is one of five centers nationwide that participate in this program.
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