Cloned, i.e. defined, defective interfering (DI) influenza A virus is produced in embryonated hens eggs using a method which generates large quantities of DI virus material. Cloned DI virus is then used in tests on mice and ferrets given a lethal challange of wild-type influenza A virus. When cloned DI influenza A virus is co-administered with a lethal dose of virulent influenza A virus, mice are protected compared to a control of inactivated cloned DI influenza A virus. Mice which survived the administration of cloned DI influenza A virus and infective challange virus are three weeks later still protected against lethal challange with infective virus. Control mice which received only cloned DI influenza A virus and no lethal challange are not protected three weeks later on lethal challange with infective virus. A therapeutic benefit of administering cloned DI influenza A virus is found when the administration takes place in less than 48 hours after challange with infective virus. Cloned DI influenza A virus of one subtype is found to act in vivo as an effective antiviral against the same or any other sub-type of influenza A virus. The antiviral effect has been found to have both a therapeutic and a prophylactic application against influenza A infection in humans, mammals and birds.
