Modified poxviruses, including modified smallpox virus vaccine based on recombinant drug-sensitive vaccinia virus, and new selection methods

摘要

The present invention provides recombinant poxviruses, such as vaccinia virus, that contain an integrated exogenous sequence, such as a foreign gene, encoding a prodrug converting polypeptide that can convert a prodrug to a drug that prevents virus replication or is otherwise toxic to the virus. The recombinant poxviruses can be suitable for use as vaccines. The invention also provides, among other things, methods of inhibiting virus replication, methods of vaccination and methods of treating vaccinated subjects showing signs or otherwise at risk for of vaccination-induced disease.

主权项

1. A smallpox vaccine composition for vaccinating a subject against smallpox comprising:
i) recombinant vaccinia virus having integrated into its viral genome an exogenous sequence encoding a prodrug converting polypeptide under transcriptional control of a vaccinia virus regulatory region, wherein the sequence is integrated into a non-essential intergenic region of the vaccinia virus genome, wherein the prodrug converting polypeptide converts a prodrug into a drug that inhibits viral replication; and ii) a pharmaceutically acceptable carrier, wherein the composition comprises the recombinant vaccinia virus in an amount sufficient to vaccinate the subject against smallpox.