Development of a marker foot and mouth disease virus vaccine candidate that is attenuated in the natural host

摘要

We have generated novel molecularly marked FMDV A24LL3DYR and A24LL3BPVKV3DYR vaccine candidates. The mutant viruses contain a deletion of the leader coding region (LL) rendering the virus attenuated in vivo and negative antigenic markers introduced in one or both of the viral non-structural 3Dpol and 3B proteins. The vaccine platform includes unique restriction endonuclease sites for easy swapping of capsid proteins for different FMDV subtypes and serotypes. The mutant viruses produced no signs of FMD and no shedding of virulent virus in cattle. No clinical signs of disease or fever were observed and no transmission to in-contact animals was detected in pigs inoculated with live A24LL3DYR. Cattle immunized with chemically inactivated vaccine candidates showed an efficacy comparable to a polyvalent commercial FMDV vaccine. These vaccine candidates used in conjunction with a cELISA provide a suitable target for DIVA companion tests.

主权项

1. An isolated DNA molecule comprising a sequence encoding a genetically marked Foot and Mouth Disease Virus (FMDV) comprising a deletion of the Lpro coding sequence, inclusion of unique restriction endonuclease sites to facilitate the replacement of the FMDV capsid region, and a negative marker mutation introduced in the non-structural viral protein 3Dpol, said mutation being the replacement of amino acids His27 and Asn31 of FMDV 3Dpol with the amino acids Tyr and Arg of the 3Dpol of Bovine Rhinovirus type 2 (BRV2).