VACCINES PREPARED FROM CHIMERAS OF FOOT-AND-MOUTH-DISEASE VIRUS (FMDV) INDUCE NEUTRALIZING ANTIBODIES AND PROTECTIVE IMMUNITY TO MULTIPLE SEROTYPES OF FMDV

The G-H loop of VP1 (residues 132 to 159) of foot-and-mouth disease vi rus (FMDV) is a prominent feature on the virion surface and has an imp ortant role in vaccine efficacy, generation of antigenic variants, and cell binding. Using in infectious cDNA of FMDV,we have constructed se rotype A viruses in which the G-H loop has been substituted with the h omologous sequences from serotype O or C. These chimeric viruses repli cated td:high titer and displayed plaque morphologies similar to those of wild-type viruses, demonstrating that the functions provided by th e loop can be readily exchanged between serotypes. Monoclonal antibody analyses showed that epitopes contained within the loop were transfer red to the chimeras and that epitopes encoded by the type A backbone w ere maintained. Chemically inactivated vaccines prepared from chimeric viruses induced antibodies in guinea pigs that neutralized both type A and either type O or type C viruses. Swine inoculated with the A/C c himera vaccine also produced cross-reactive antibodies, were protected from challenge with the type A virus, and partially protected against challenge with type C. These studies emphasize the importance of epit opes outside of the G-H loop in protective immunity in swine, which is a natural host of FMDV.