Strategy for construction of live picornavirus vaccines.

A number of recombinant viruses between the virulent Mahoney and the attenuated Sabin 1 strains of type 1 poliovirus were constructed in vitro using their infectious cDNA clones. Monkey neurovirulence tests on these recombinant viruses revealed that the surface structure of the virion particle had a little correlation with the neurovirulent phenotype, and that the strong neurovirulence determinant(s) resided in the 5' noncoding sequence. These results in turn led to two possible strategies for constructing live attenuated picornavirus strains. One is to use the Sabin 1 strain as a vector carrying foreign antigenicities. The other is the construction of the attenuated picornaviruses by introducing mutations into the 5' noncoding sequences. The antigenicity of the Sabin 1 strain was successfully changed to those of other poliovirus serotypes without loss of vaccine quality. Furthermore, it was proved that introduction of deletion mutation into the 5' noncoding sequence of genomes of the Sabin 1 and Mahoney strains resulted in construction of viruses with a less neurovirulent phenotype.