Nigeria Sabin-like poliovirus (complete genome). Human Poliovirus

To assess the dynamics of genetic reversion of live poliovirus vaccine in humans, we studied molecular evolution in Sabin-like poliovirus isolates from Nigerian acute flaccid paralysis cases obtained from routine surveillance. We employed a novel modeling approach to infer substitution and recombination rates from whole-genome sequences and information about poliovirus infection dynamics and individual vaccination history. We confirmed observations from a recent vaccine trial that VP1 substitution rates are increased for Sabin-like isolates relative to the wild-type rate due to increased non-synonymous substitution rates. We also inferred substitution rates for attenuating nucleotides and confirmed that reversion can occur in days to weeks after vaccination. We combine our observations for Sabin-like evolution with the wild-type circulating VP1 molecular clock to infer that the mean time from the initiating vaccine dose to the earliest detection of circulating vaccine-derived poliovirus (cVDPV) is 300 days for type 1, 210 days for type 2, and 390 days for type 3. Phylogenetic relationships indicated transient local transmission of Sabin 3 and possibly Sabin 1 during periods of low wild polio incidence. Comparison of Sabin-like recombinants with known Nigerian VDPV recombinants shows that while recombination with non-Sabin enteroviruses is associated with cVDPV, the recombination rates are similar for Sabin-Sabin and Sabin-non-Sabin enterovirus recombination after accounting for time from dose to detection. Our study provides a comprehensive picture of the evolutionary dynamics of oral polio vaccine in the field.