In September 2024, circulating vaccine-derived poliovirus type 2 (cVDPV2) was detected in wastewater from Barcelona. The detected strain was genetically linked to the Nigerian NIE-ZAS cVDPV2.

We describe the mutational and phenotypic landscape of the VP1 genome swarm present in Barcelona sewage, representing the ensemble of viral variants shed by the infected population. In total, 1.030 haplotypes were identified: one dominant haplotype accounting for 66% of all reads, 57 haplotypes representing 17%, and the remaining 972 haplotypes accounting for the final 17%. The dominant haplotype harboured 48 mutations, eight of which were nonsynonymous, whereas most other haplotypes contained 49–52 mutations, with 9–10 nonsynonymous changes. Most of these mutations mapped to antigenic sites that overlap with the receptor-binding domain. Using dynamic computational models of antibody and receptor interactions, we found that most haplotypes exhibited a significant reduction in antibody binding, while only a small fraction showed increased receptor binding. Although observed in only 0.5% of sequences, the highly concerning combination of antibody escape and enhanced receptor binding underscores the need for continued and intensive surveillance.