Oral poliovaccine: will it help eradicate polio or cause the next epidemic?

BACKGROUND Poliovirus rapidly evolves by nucleic acid substitutions and genetic recombination with other polioviruses and non-polio enteroviruses. Evolving oral poliovaccine can rapidly revert to neurovirulence and undergo antigenic alterations. OBJECTIVES To evaluate the threat of vaccine-derived poliovirus (1-15% divergence from the respective Sabin strain) for a poliomyelitis-free population in a country with a long-standing routine vaccination program. METHODS We characterized genetic and antigenic changes in OPV (Sabin) strains isolated from sewage in Israel and evaluated intestinal immunity by measuring fecal excretion after OPV challenge of vaccinated children. RESULTS Characterization of poliovirus from sewage revealed eight type 2 and three type 3 vaccine polioviruses that had replicated and started to evolve (vaccine that replicated and diverged by 0.5 to < or = 1.0%) and nine highly diverged type 2 vaccine-derived polioviruses (1-15% divergence from the respective Sabin strain) with 8-14% divergence between the years 1998 and 2005. Six of the eleven VRPV uniquely recombined with OPV and/or NPEV. The nine VDPV were epidemically related, genotypically neurovirulent, and had 10-15 amino acid substitutions in antigenic sites altering their antigenicity, but shared a single recombination. Type 2 OPV was excreted by 23% and 17% of infants challenged with OPV 3 months after partial immunization (two doses each of OPV and enhanced inactivated poliovirus) or full immunization (three doses of each) respectively, despite high humoral antibody titers. CONCLUSIONS Our findings, which show that OPV is excreted for a significant period by children with high humoral immunity, emphasize the long-term potential threat from VDPV in highly vaccinated populations. An adequate immunization program, combined with environmental surveillance, is necessary to prevent poliomyelitis and community transmission of poliovirus.