Higher stability of novel live-attenuated oral poliovirus type 2 (nOPV2) despite the emergence of a neurovirulent double recombinant strain in Uganda

The novel oral poliovirus vaccine type 2 (nOPV2) was developed to reduce the risk of circulating vaccine-derived poliovirus outbreaks by incorporating genetic modifications to enhance genetic stability and reduce reversion to virulence while retaining protection. Here we report the characterization of 231 nOPV2 isolates from Uganda during a 1-year period following nOPV2 use. Whole-genome sequencing revealed that most isolates retained nOPV2's genetic modifications, with limited mutations in the VP1 region indicating no relevant virus transmission. However, a double recombinant strain identified in a sewage sample lost all key nOPV2 modifications through recombination with enterovirus C strains upstream and downstream of the capsid coding region. This resulted in high neurovirulence comparable to that of wild-type 2 poliovirus. Despite this, the strain did not spread widely, probably due to high vaccination coverage. These findings underscore the enhanced genetic stability of nOPV2 and its reduced risk of reversion compared with Sabin monovalent OPV2 (mOPV2), while highlighting the importance of surveillance to detect rare recombination events. Continued use of nOPV2 and inactivated polio vaccine, combined with robust immunization and monitoring, remains essential for achieving and sustaining global polio eradication.