Whole Genome Characterization of Rotavirus Group A Strains Isolated from Children Admitted in Kilifi County Hospital Following Routine Vaccination in Kenya

Abstract

The introduction of rotavirus vaccines into national immunization programmes (NIPs) of many countries globally has considerably reduced the rotavirus group A (RVA) disease burden. Kenya introduced the monovalent Rotarix® vaccine (G1P[8] backbone) into its national immunization programme in July 2014 and a ~60% decrease in rotavirus group A-associated diarrhoea hospitalization was reported two years post-vaccine introduction. Despite this success, rotavirus group A continues to be among the leading causes of severe diarrhoea in young children hospitalized at Kilifi County Hospital (KCH) on the coast of Kenya. Coincidentally, studies elsewhere have shown an increase in Rotarix® vaccine partially or fully heterologous genotypes in countries implementing Rotarix® vaccine use. Therefore, this study aimed to study the genetic relatedness, origin, and evolution of rotavirus group A G2P[4] strains circulating in the Rotarix® pre- and post-vaccination period in Kilifi County and determine whether the introduction of the Rotarix® vaccine in Kenya impacted the antigenic diversity of G2P[4] RVA strains circulating in Kilifi County, coastal Kenya. Whole genome sequencing of 32 pre-(January 2012 to June 2014) and 31 post-vaccine -(July 2014- December 2018) periods rotavirus group A G2P[4] vaccine heterologous strains infecting children (<13 years old) admitted to KCH was done to understand the genetic diversity of these strains and determine their potential origins (source) and local transmission patterns. The results found that both pre- and post-vaccine G2P[4] strains had a typical DS-1-like genomic backbone (G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2). The Kilifi G2P[4] strains classified into lineages II (for VP4 segment), lineage IV (for VP7, VP4, VP2, NSP1, and NSP5 sequences), lineage V (for VP6, VP1, VP3, NSP2, and NSP3 segments), lineage VI (for the NSP4 segment) and lineage VII (for the VP3 and NSP4 segments). Phylogenetically, the Kilifi pre- and post-vaccine period sequences majorly formed separate clusters on the global phylogeny across the 11 genome segments, implying distinct virus populations were in circulation pre- and post-vaccine periods. In addition, the Kilifi strains mainly clustered on the same branch separate from other global strains, suggesting observed local strains were most likely persisting in the Kilifi or surrounding regions with an accumulation of genetic changes over time. However, the Kilifi pre- and post-vaccine strains had conserved amino acid changes on the antigenic epitopes of the VP7 and VP4 surface proteins, suggesting that replacement of the pre-vaccine population was unlikely due to immune escape. In conclusion, the study indicated that the G2P[4] strains circulating in Kilifi pre- (January 2012 to June 2014) and post-(July 2014- December 2018) periods are genetically different but antigenically similar and constitute locally circulating strains. Further studies should be conducted to determine the genomic epidemiology of G2P[4] strains by extending the geographical sampling area by including various health facilities across Kenya and from non-hospitalized infected persons in the community to have a representative sample across the entire Kenyan population.