EVALUATION OF A LIVE-ATTENUATED FOOT-AND-MOUTH-DISEASE VIRUS AS A VACCINE CANDIDATE

A variant of foot-and-mouth disease virus (FMDV) lacking the leader (L ) coding region (A12-LLV2) was previously constructed and shown to he less Virulent in cattle than its wild-type parent (A12-IC). In this st udy, cattle were tested for their clinical and immunological responses to subcutaneous inoculation with A12-LLV2 or A12-IC or to intramuscul ar vaccination with chemically inactivated A12-IC. Five weeks postinoc ulation animals were challenged by intradermal inoculation in the tong ue with a Virulent cattle-passaged virus. A12-LLV2-inoculated animals showed no clinical signs of disease and developed a neutralizing antib ody response by 4 days postinoculation, whereas a companion control bo vine did not seroconvert After challenge, two of three inoculated anim als did not develop lesions, but showed mild signs of infection. The t hird inoculated animal developed some lesions, but these were less sev ere than in the uninoculated control animal, which showed classical FM D. All animals inoculated with A12-IC developed a fever, two showed ty pical FMD lesions, and the companion control seroconverted, indicating that it had acquired infection by contact The Ala-IC-inoculated anima ls and the control were protected from challenge. Animals Vaccinated w ith inactivated virus showed no clinical signs of disease and develope d a neutralizing antibody response, and the control did not seroconver t Upon challenge none of the vaccinated animals developed lesions, one developed a fever, and the control developed FMD. These experiments d emonstrate the potential of a rationally designed live-attenuated FMDV vaccine. (C) 1997 Academic Press