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.
• 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.