Emergence of vaccine-derived poliovirus strains from the novel oral polio vaccine in the Central African Republic.

UNLABELLED: The Central African Republic (CAR) is a high-risk country for poliomyelitis outbreaks because of difficulties in closing immunity gaps due to the lack of resources, logistics issues, and insecurity. The country experienced multiple poliomyelitis cases since 2019. A novel type 2 oral polio vaccine (nOPV2) engineered to lower the risk of reversion of the vaccine strain was deployed in the CAR in 2022-2023 to counter active serotype 2 poliovirus transmission. This study reports routine poliovirus surveillance conducted from November 2021 through October 2023 in the CAR. Polioviruses isolated from stools and wastewater were genetically characterized based on the VP1-encoding region that was sequenced by Sanger technique. Whole-genome sequencing was conducted on all nOPV2-derived isolates and on a subset of Sabin-2-derived isolates by using Illumina technology. Fifty-four vaccine-derived poliovirus type 2 isolates were identified, belonging to eight distinct emergences: four emergences were derived from the historical vaccine strain and four from the nOPV2. The nOPV2 derivatives that had kept the original 5' untranslated region (5'UTR) did not display any reversions in the modified domain V, which is the primary attenuation site. Nonetheless, some nOPV2 derivatives had lost this domain through recombination with members of species Enterovirus coxsackiepol (EV-C). Our analyses demonstrate that recombination took place shortly after the vaccine rollout. The data demonstrate that nOPV2's genetic stabilization curtails genetic drift-driven reversion but does not eliminate recombination. This underscores the need for comprehensive EV-C surveillance alongside poliovirus monitoring, especially in Sub-Saharan Africa where they are relatively abundant.

IMPORTANCE: The novel oral polio vaccine of serotype 2 (nOPV2) was engineered to prevent the emergence of revertant polio vaccine strains, which caused numerous outbreaks in the 2000s and 2010. Since 2021, it has been used in many countries, especially in Sub-Saharan Africa, to contain poliomyelitis outbreaks. In 2023, double recombinant nOPV2-derived isolates that had lost all the attenuation determinants were detected in the Central African Republic (CAR). Several of these were the first nOPV2 revertant isolates ever reported to the Global Polio Eradication Initiative, thereby demonstrating that the engineered modifications in nOPV2 do not entirely prevent reversion via recombination with non-polio enteroviruses of species Enterovirus coxsackiepol (EV-Cs). This study corroborates the increased genetic stability of nOPV2 compared to the historical vaccine strain but demonstrates that reversion through recombination with non-polio EV-Cs remains possible. This underscores the need for comprehensive EV-C surveillance alongside poliovirus monitoring, especially in Sub-Saharan Africa where EV-Cs are particularly abundant. In particular, assessing EV-C potential seasonal circulation patterns could inform the design of vaccination strategies tailored to minimize the risk of recombination between nOPV2 and non-polio EV-Cs.