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  • Title: Genetic basis of attenuation of the Sabin type 2 vaccine strain of poliovirus in primates.
    Author: Macadam AJ, Pollard SR, Ferguson G, Skuce R, Wood D, Almond JW, Minor PD.
    Journal: Virology; 1993 Jan; 192(1):18-26. PubMed ID: 8390752.
    Abstract:
    The type 2 live-attenuated vaccine strain of poliovirus (P2/Sabin) is associated with rare cases of poliomyelitis in vaccinees or their contacts. Recombinants were generated between infectious clones of a neurovirulent isolate from one such case (P2/117) and P2/Sabin and neurovirulence assays suggested that a maximum of six nucleotide differences between the two strains were responsible for their phenotypic difference. Site-directed mutagenesis of P2/Sabin showed that mutations at just two positions, at 481 in the 5' non-coding region and at VP1-143 in the capsid proteins, resulted in a highly neurovirulent virus. Other nucleotide changes may have weaker phenotypic effects. These results are consistent with those reported in the mouse model by Ren et al. [J. Virol. 65, 1377, (1991)] indicating that, for P2/Sabin at least, the same determinants of attenuation are important in both primates and transgenic mice expressing the poliovirus receptor. Sequence analysis of isolates from other vaccine-associated cases of poliomyelitis and from healthy vaccinees showed that both major determinants of attenuation are unstable on human passage, although selection pressures against an A at 481 are stronger than those against an Ile at 1143.
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