Proof-of-concept studies suggest that current defences against
smallpox could be strengthened by supplementing vaccination with
antiviral drug prophylaxis, based on aerosolized or orally available forms of the long-acting medication
cidofovir. Delivery of aerosolized
cidofovir to mice results in its prolonged retention in respiratory tissues and protection against lethal intranasal or
aerosol poxviral challenge. Although
cidofovir itself is not orally available, the addition of an alkoxyalkanol
ether side-chain allows it to be absorbed from the gastrointestinal tract. This also markedly increases its
antiviral activity and lengthens its intracellular half-life from roughly 3 to 8-10 days. Oral treatment also protected mice against lethal poxviral challenge. These results suggest that a single
aerosol dose of
cidofovir (or an alkoxyalkanol-
ether derivative) could provide prolonged protection against initiation of
smallpox infection, whereas oral treatment could prevent both initiation of
infection and internal dissemination of virus. Both approaches may avoid the nephrotoxicity that occasionally results from intravenous
cidofovir therapy.