CONSTRUCTION AND EVALUATION OF AN ATTENUATED VACCINE FOR FOOT-AND-MOUTH-DISEASE - DIFFICULTY ADAPTING THE LEADER PROTEINASE-DELETED STRATEGY TO THE SEROTYPE O1 VIRUS

Over the last few years we have utilized a system to genetically engin eer foot-and-mouth disease virus (FMDV) to produce live-attenuated vac cine candidates. These candidates have been generated in the genetic b ackground of a tissue culture-adapted strain of serotype A12 virus. Ba sed on this A12 system, we created a virus lacking the sequence encodi ng the leader (L) proteinase (Piccone et al., 1995), and demonstrated that this leaderless virus, A12-LLV2 was avirulent in bovine and swine , and could be used as an attenuated vaccine (Mason et al., 1997; Chin sangaram et al., 1998). The current study shows that a similar leader- deleted chimeric virus containing the genome of the type A12 virus wit h a substituted type O1 capsid coding region from a bovine-virulent vi rus can be constructed, and that the virus has low, but detectable vir ulence in swine. A second: chimera specifying a tissue culture-adapted type O1 capsid lacking the RGD cell binding site, was avirulent in sw ine, but was not sufficiently immunogenic to provide protection from c hallenge. These results are described with respect to mechanisms of at tenuation and antigen formation in live-attenuated virus-inoculated an imals. Published by Elsevier Science B.V.