Genomic epidemiology reveals post-vaccine re-emergence of vaccine-associated G1P[8] rotavirus lineages with variable disease severity

Summary Group A rotavirus G1P[8] strains, which are targeted by the Rotarix vaccine, have persisted in several countries following the introduction of the Rotarix vaccine. However, the evolutionary origins of the persisting strains remain unclear. Here, we leveraged over two decades of rotavirus surveillance data from Malawi to understand the genomic epidemiology of G1P[8] strains in a high-disease-burden sub-Saharan African setting. We observed a reversion of G1P[8] strains to the conventional Wa-like genotype constellation identified pre-vaccination, following transient circulation of DS-1-like G1P[8] strains. Most G1P[8] lineages that re-emerged post-vaccination circulated before vaccine introduction. Furthermore, new strains emerged post-vaccination through re-assortment of pre-existing viruses. The predominant post-vaccination lineage (MW-VP7-L2) contained an N147D substitution at an antigenically important site of the VP7 glycoprotein and showed evidence of episodic diversifying selection. Children infected with the MW-VP7-L2 lineage had a higher severity score of gastroenteritis than infections with other co-circulating lineages. These findings highlight the importance of long-term genomic surveillance to understand rotavirus transmission, evolution, and disease severity, and to guide public health interventions.