WHOLE GENOME CHARACTERIZATION OF ROTAVIRUS GROUP A G1P[8] STRAINS IN KILIFI, KENYA, BEFORE AND AFTER VACCINE INTRODUCTION

Abstract

Group A rotaviruses (RVA) are a leading cause of severe acute gastroenteritis in young children worldwide. Kenya introduced the monovalent Rotarix® vaccine (derived from a live attenuated G1P[8] rotavirus strain) in July 2014. Continual RVA surveillance in Kilifi (coastal Kenya), between 2010 – 2019 showed that RVA G1P[8] strains predominated during both the pre- and post-vaccine introduction periods. This project aimed to determine the patterns of genome-wide variation and evolution of G1P[8] strains collected in Kilifi Kenya before and after the Rotarix® vaccination program took effect. Here, analysis of 171 full-length RVA genomes identified that the pre- and post-vaccine strains possessed the typical Wa-like genogroup constellation (G1-P[8]-I1-R1-C1-M1- A1-N1-T1-E1-H1) and presence of intra-genogroup reassortant genotype. Phylogenetic analysis revealed that post-vaccine strains were genetically distinct from pre-vaccine strains and one had undergone gene reassortment. Genetic analysis revealed multiple amino acid differences between pre- and post-vaccine introduction strains across the entire genome. Pairwise analysis of the surface proteins VP7 and VP4 antigenic regions revealed multiple amino acid differences between the strains and the Rotarix vaccine. Bayesian analysis revealed that the pre- and post-vaccine strains diverged long (1988-1995) before vaccine implementation in Kenya. Taken together, these findings indicate that the post vaccine G1P[8] strains were separately introduced into this population and that their genetic diversity is unlikely to be as a result of vaccine driven immune pressure but natural strain evolution. This study illustrates the importance of genomic surveillance in monitoring evolution of rotaviruses and in providing crucial information on the impact of vaccine introduction on circulating strains diversity