question: To protect layers, breeders and grandparents against damage by infectious bronchitis virus infections during the laying period, vaccination using live priming followed by a boost with inactivated IB vaccine is commonly used For many IB variants, homologous live vaccines are not available for priming Very little is known about the efficacy of priming with heterologous live IB vaccines (or combination of live IB vaccines) to induce broad IB protection in long-living chickens In this study, the protection levels induced by vaccination programmes with only heterologous live priming by a Massachusetts vaccine and a 4/91 vaccine, only a multivalent inactivated vaccine that contained D1466 antigen and a combination of both, against a D1466 challenge were compared The infection with infectious bronchitis virus D1466, a genotype II, lineage 1 virus, was able to cause serious damage to the unvaccinated laying hens resulting in respiratory signs, a long-lasting drop in egg production and loss of egg quality All three vaccination programmes induced significant levels of protection against challenge with a pathogenic D1466 strain Overall, the vaccination programme using the broad heterologous live priming and the inactivated vaccine provided high protection against the combination of egg drop and loss of egg quality The results showed that this combination of heterologous live vaccines was able to increase the efficacy of the inactivated infectious bronchitis virus vaccine despite the very low antigenic relationship of both live vaccines with the challenge strain