Evolution of the Sabin strain of type 3 poliovirus in an immunodeficient patient during the entire 637-day period of virus excretion

A 20-year-old female hypogammaglobulinemic patient received monotypic Sabin 3 vaccine in 1962. The patient excreted type 3 poliovirus for a period of 637 days without developing any symptoms of poliomyelitis, after which excr etion appeared to have ceased spontaneously. The evolution of Sabin 3 throu ghout the entire period of virus excretion was studied by characterization of seven sequential isolates from the patient. The isolates were analyzed i n terms of their antigenic properties, virulence, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin t ype 3 vaccine. The isolates followed a main lineage of evolution with a rat e of nucleotide substitution that was very similar to that estimated for wi ld-type poliovirus during person-to-person transmission. There was a delay in the appearance of antigenic variants compared to sequential type 3 isola tes from healthy vaccines, which could be one of the possible explanations for the long-term excretion of virus from the patient. The distribution of mutations in the isolates identified regions of the virus possibly involved in adaptation for growth in the human gut and virus persistence. None of t he isolates showed a full reversion of the attenuated and temperature-sensi tive phenotypes of Sabin 3. Information of this sort will help in the asses sment of the risk of spread of virulent polioviruses from long-term excreto rs and in the design of therapies to stop long-term excretion. This will ma ke an important contribution to the decision-making process on when to stop vaccination once wild poliovirus has been eradicated.