Since 1998, nine of the 26 serotypes of bluetongue virus (BTV) have spread throughout Europe and serotype 8 has suddenly emerged in northern Europe causing considerable economic losses, both direct (mortality and morbidity) but also indirect due to restriction in animal movements. Therefore many new types of vaccines, particularly subunit vaccines, with improved safety and efficacy for a broad range of BTV serotypes are currently being developed by different laboratories. Here we exploited a reverse genetics-based replication-deficient BTV-1 serotype (disabled infectious single cycle, DISC) to generate a series of DISC vaccine strains. Cattle and sheep were vaccinated with these viruses either singly or in cocktail as multivalent vaccine candidate. All vaccinated animals were seroconverted and developed a neutralizing antibody response against their respective serotype. After challenge with the virulent strains at 21 days post vaccination vaccinated animals showed neither any clinical reaction nor viremia. Further, there was no interference in protection with a multivalent preparation of six distinct DISC viruses. These data indicate that a very rapid response vaccine could be developed based on which serotypes are circulating in the population at the time of an outbreak.