Genetic basis for immunological aberrations in poliovirus Sabin serotype 3 strains imported in the netherlands

Abstract

During the characterization of poliovirus type 3 strains imported in The Netherlands, Sabin serotype 3 strains that reacted with both specific antisera against Sabin-like (vaccine) and non-Sabin-like (wild-type) strains by the intratypic strain differentiation assay have been found. The present study was done to determine the pathogenic potential of these virus strains for humans. Characterization of these so-called double-reactive strains with neutralizing monoclonal antibodies (MAbs) against the major antigenic sites of serotype 3 Sabin virus led to the identification of two groups with different antigenic properties. Six of the seven strains were resistant to neutralization 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 strain was identified as highly neurovirulent, three were identified as intermediate, and three were identified as attenuated. Sera from vaccinated persons efficiently neutralized the mutants. Our data suggest that some double-reactive strains are a potential risk to the unvaccinated community but not to the vaccinated population.

FIG. 1

Locations of sequenced regions on the poliovirus type 3 genome. Seq., sequence; ∗, antigenic sites according to Minor et al. (14).

FIG. 2

Average absorption ratios of poliovirus serotype 3 Sabin site 3B escape mutant (strain 4022), a prototype serotype 3 NSL strain (strain Saukett), and a prototype serotype 3 SL strain (strain Sabin) by ITSD-E. Virus strains with ratio of >2.5 are classified as SL strains, those with ratios of <0.5 are classified as NSL strains, and those with ratios of <2.5 and >0.5 are classified as DR. ∗, P < 0.05.

FIG. 3

Neutralization ratios for IPV- and OPV-vaccinated blood donors against prototype and DR strains with amino acid substitutions in antigenic site 3B. Ratios are expressed as the titer of neutralizing antibodies when Sabin serotype 3 or a DR strain was used as challenge virus divided by the titer obtained when the Saukett strain was used as the challenge virus.

FIG. 4

Replication differences for DR strains on HEp-2c cells at 37 and 40°C after 4 h postinfection expressed as the difference in virus titer obtained when cells were incubated at 37 or 40°C.