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Virology. 1993 Jan;192(1):18-26.

Genetic basis of attenuation of the Sabin type 2 vaccine strain of poliovirus in primates.

Author information

1
National Institute for Biological Standards and Control, Potters Bar, Herts, United Kingdom.

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.

PMID:
8390752
DOI:
10.1006/viro.1993.1003
[Indexed for MEDLINE]

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