Genetic basis for immunological aberrations in poliovirus Sabin serotype 3strains imported in The Netherlands

During the characterization of poliovirus type 3 strains imported in The Ne therlands, Sabin serotype 3 strains that reacted with both specific antiser a against Sabin-like (vaccine) and non-Sabin-like (wild-type) strains by th e intratypic strain differentiation assay hale been found. The present stud y was done to determine the pathogenic potential of these virus strains for humans. Characterization of these so-called double-reactive strains with n eutralizing monoclonal antibodies (MAbs) against the major antigenic sites of serotype 3 Sabin virus led to the identification of two groups with diff erent antigenic properties. Six of the seven strains were resistant to neut ralization with MAbs against sites 2B and 3B and one strain was neutralized by all the MAbs in a manner similar to that for the Sabin serotype 3 virus . Partial sequencing of the coding regions confirmed the antigenic changes for all six antigenically distinct strains. By inoculation of these viruses into transgenic mice which express the human poliovirus receptor, one stra in was identified as highly neurovirulent, three were identified as interme diate, and three were identified as attenuated. Sera from vaccinated person s efficiently neutralized the mutants. Our data suggest that some double-re active strains are a potential risk to the unvaccinated community but not t o the vaccinated population.