POTENTIAL USE OF POLIOVIRUS AS A VECTOR

The live attenuated Sabin strains of poliovirus have proven their efficacy at inducing a good humoral and secretory antibody response in humans. The extensive characterization of poliovirus neutralization antigenic sites and the atomic resolution of the three-dimensional structure of the viral capsid have enabled the use of the most stably attenuated poliovirus strain (the Sabin type 1 strain) as a vector for the presentation of short foreign antigenic domains in place of one of its own neutralization antigenic sites. The creation of such chimeras has been achieved by manipulating poliovirus infectious cDNA and transfecting the resulting chimeric cDNAs onto susceptible cell cultures. However, this epitope-presentation system has a limitation in terms of the sequence and size of the foreign domain that can be incorporated into the poliovirus capsid without disrupting virus viability. This has led to the construction of poliovirus hybrid genomes bearing insertions of longer heterologous sequences in place of part of the poliovirus structural genes. Upon transfection onto susceptible cells providing the poliovirus structural proteins in trans (e.g. cells previously infected with the Sabin 1 strain), stocks of encapsidated RNA replicons which expressed the foreign protein could be obtained. In addition, viable recombinant viruses bearing insertions of heterologous sequences at various places into the poliovirus genome without deleting poliovirus sequences have been reported. Potential applications of these chimeric and recombinant polioviruses in the engineering of new recombinant vaccines are discussed. © 1993 by Academic Press, Inc.