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Coronavirus Biology and Pathogenesis
On the Front Lines
Approaches to Vaccines and Drug Development
Blocking SARS Virus Fusion
Lessons in Interventions for SARS
Status of Drug Screening vs. SARS
Adenovirus Vector Technologies for Vaccines
Some Approaches to Vaccine Development
Panel 3 Discussion
Future Perspectives on Emerging Infections
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SARS in the Context of Emerging Infectious Threats SARS in the Context of Emerging Infectious Threats
Approaches to Vaccines and Drug Development
Lessons in Interventions for SARS

Frederick Hayden, University of Virginia School of Medicine, Charlottesville
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Highlights

Current Vaccines and Antivirals in Humans
• Inactivated vaccines for flu induce strain-specific durable immunity and antibody to hemmaglutanin correlates with protection, but the virus changes rapidly.
• Natural infections induce incomplete protection against RSV and human CoVs, so repeat infections occur.
• Monoclonals to RSV fusion protein effective against lower respiratory tract disease in high-risk infants.
• Formalin-inactivated whole virus vaccine against RSV-induced aberrant immune responses and worse outcomes in infants in the 1960s.
• There is no proven vaccine or antiviral for human respiratory CoVs.
• Effective application of these modalities is important.

Flu Antivirals
• Development of neuraminidase inhibitors has been rapid when linked to virologic and clinical surveillance, access to populations, and accurate diagnosis.
• Antivirals may be an adjunct to or substitute for vaccine, offering several strategies that may be applicable to SARS.
• Oseltamivir reduces risk of hospitalization by half.
• Using treatment of an index case and close contacts with neuraminidase inhibitors, no resistance or transmission occurred.

Current Drugs used for SARS
• The sequence of viral load from low to peak at day 10 and subsequent decline offers a window of opportunity for antiviral intervention.
• Corticosteroids may have contributed to protracted and increased viral replication.
• Dexamethasone causes a delay in clearance of respiratory syncytial virus in infants.
• Steroids enhance replication and mortality in mice with pneumonia.
• Intranasal steroids delay viral clearance in rhinovirus in adulty and increase the risk of acute otitis media in children.
In vitro assays show no inhibition of SARS coronavirus replication by ribavirin.

Interferon protection for CoVs
• Alpha and beta interferon have activity against SARS CoV when screened in vitro.
• Intranasal interferon at a relatively high dose (common cold unit) shows 55 percent reduction of infection and 85 percent reduction of development of colds.
• Lower doses of intranasal interferon did not protect against infection but moderated the frequency of colds.
• Need to understand whether there are over-exuberant or deficient responses in SARS that may be supplemented.
• Controlled clinical trials will be essential.

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