Key result
CHAT and Cox strains exhibited lower temperature sensitivity and higher neurovirulence than Sabin 1, and analysis of CHAT-related VAPP isolates revealed genetic reversions to wild-type sequences and recombination with Sabin 3.
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May guide safer live poliovirus vaccine design; leaves open recombination risks in modern strains.
CHAT and Cox type 1 live-attenuated poliovirus strains were developed in the 1950s to be used as vaccines for humans. This paper describes their characterization with respect to virulence, sensitivity for growth at high temperatures, and complete nucleotide and amino acid sequences. The results are compared to those for their common parental wild virus, the Mahoney strain, and to those for two other poliovirus strains derived from Mahoney, the Sabin 1 vaccine strain and the mouse-adapted LS-a virus. Analysis of four isolates from cases of vaccine-associated paralytic poliomyelitis related to the CHAT vaccine revealed genetic and phenotypic properties of the CHAT strain following replication in the human gut. CHAT-VAPP strain 134 contained a genome highly evolved from that of CHAT (1.1% nucleotide differences), suggesting long-term circulation of a vaccine-derived strain in the human population. The molecular mechanisms of attenuation and evolution of poliovirus in humans are discussed in the context of the global polio eradication initiative.
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Martín et al. (2002) studied Vaccine-associated paralytic poliomyelitis (n=4). CHAT and Cox type 1 live-attenuated poliovirus vaccine strains vs. Mahoney strain and Sabin 1 strain was evaluated on Genetic and phenotypic properties (neurovirulence, temperature sensitivity, nucleotide sequences). CHAT and Cox strains exhibited lower temperature sensitivity and higher neurovirulence than Sabin 1, and analysis of CHAT-related VAPP isolates revealed genetic reversions to wild-type sequences and recombination with Sabin 3.
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