Evolution of the live-attenuated novel oral poliovirus type 2 (nOPV2) vaccine: detection of a 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. Following nOPV2’s Emergency Use Listing authorization by WHO in 2020, the genetic stability of nOPV2’s main attenuation site was confirmed by whole genome sequencing of multiple nOPV2 isolates during the initial use phase (March-October 2021) in various countries. Uganda conducted two nationwide nOPV2 campaigns in 2022 and successfully interrupted cVDPV2 transmission identified in Lubigi sewage treatment plant in November 2021. This study reports the characterization of 233 nOPV2 isolates from Uganda during a one-year period following nOPV2 use, focusing on the analysis of nOPV2 genetic stability and the identification of a rare double recombinant strain. 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 from Kabarole in February 2022 lost all key nOPV2 modifications through recombination with enterovirus C strains upstream and downstream of the capsid coding region, resulting in high neurovirulence comparable to wild-type 2 poliovirus. Despite this, the strain did not spread widely, likely due to high vaccination coverage. These findings underscore the enhanced genetic stability of nOPV2 and its reduced risk of reversion compared to Sabin monovalent OPV2 (mOPV2), while highlighting the importance of vigilant surveillance to detect and respond to rare recombination events. Continued use of nOPV2 and inactivated polio vaccine (IPV), combined with robust immunization and monitoring, remains essential for achieving and sustaining global polio eradication.