Moderated by Dr. Scott Hammer
Click on the titles at the left to view the video, transcript, slides, and
text highlights from each speaker's presentation.
David Ho, Aaron Diamond AIDS Research Center, New York
Blocking SARS Virus Fusion
Frederick Hayden, University of Virginia School of Medicine, Charlottesville
Lessons in Interventions for SARS
Catherine Laughlin, National Institute of Allergy and Infectious Diseases, Bethesda
Status of Drug Screening vs. SARS
C. Richter King, GenVec Inc., Gaithersburg, VA
Adenovirus Vector Technologies for Vaccines
Thomas Monath, Acambis, Cambridge, MA
Some Approaches to Vaccine Development
Panel 3 Discussion, with Richard Colonno (Bristol-Myers Squibb), Michael Dunne (Pfizer), and Emilio Emini (Merck)
Despite more than two decades of research, the clever HIV pathogen has continued to elude us. But some new good may come out of all those years of study: The coronavirus that causes SARS appears to fuse to host cells in much the same way as HIV. Harnessing this knowledge, David Ho, M.D., scientific director of the Aaron Diamond AIDS Research Center at The Rockefeller University—who has scrutinized HIV for 22 years—and his team have designed a peptide that may inhibit this fusion. Preliminary studies in Hong Kong are producing promising results in tissue culture. Ho speculates that this peptide would have little toxicity in clinical applications. "There are still many obstacles in the way, but this is an example of what one can do in a very short time," he concluded.
Since so little is known about the virus' behavior, some doctors have been treating SARS patients with ribavirin and steroids such as dexamethasone, a treatment approach that has not been effective. In fact, corticosteroids may actually delay viral clearance in patients with viral respiratory infections, explained Frederick G. Hayden, M.D., professor of internal medicine and pathology at the University of Virginia School of Medicine. "One has to be very cautious about the effects of corticosteroids on viral replication, particularly in the absence of antiviral drugs," he asserted. Antiviral agents that appear intriguing for use in SARS patients include oseltamivir, zanamivir, and interferon. "We need a better understanding of the natural history of the infection, including mechanisms of injury and host immunopathologic responses," he added. "Controlled clinical trials are going to be essential to understand what really works in this illness."
Drugs with the potential for treating SARS will go through an intensive screening process jointly coordinated by the CDC, the U.S. Army Medical Research Institute of Infectious Diseases, and the NIAID. "There are many steps in the viral life cycle where fusion inhibitors might play a role," said Catherine Laughlin, Ph.D., chief of the Virology Branch of the Division of Microbiology and Infectious Diseases at the NIAID. Other potential drug targets include cysteine protease, RNA-dependent RNA polymerase, helicase, genome replication and transcription, and the N protein. Laughlin hypothesized that the most effective treatment will probably be a combination of an antiviral agent and another drug that interferes with the viral replication process.
The race is on between pharmaceutical companies setting out to make a name for themselves in the SARS arena. GenVec, Inc., a Maryland-based biopharmaceutical company, is developing a vaccine against SARS using its adenovector technology, in collaboration with the Vaccine Research Center of the NIAID and the U.S. Navy Medical Research Center. C. Richter King, Ph.D., vice president of research at GenVec, explained that the "AdVaccine" is based on an adenovirus that is modified to contain a therapeutic protein. The resulting adenovector bears a therapeutic gene capable of triggering an immune response. Moreover, King noted that the highly targeted vaccine is safe and well tolerated, and easily manufactured.
Acambis, a pharmaceutical company specializing in vaccine development, has begun its own investigations into a vaccine for SARS, hoping to build on the success it has had creating vaccines against smallpox and travel-related diseases. Thomas Monath, M.D., chief scientific officer at Acambis, noted the scarcity of effective vaccines to treat coronavirus infections in animals, and highlighted the need for a suitable animal model of SARS. (So far, macaque monkeys have been the only animals offering promise in this regard.) He cautioned that it could take at least five to six years to develop an effective vaccine, at a cost of some $60-100 million and requiring the collaboration of academic and industrial scientists. "We need to understand the natural history of this disease and develop appropriate animal models, and that will allow us to develop rational approaches," he advised.
The session concluded with a panel discussion that also included representatives from Bristol-Myers Squibb Company, Pfizer Inc, and Merck Research Laboratories.