Genomic epidemiology and evolutionary dynamics of respiratory syncytial virus group B in Kilifi, Kenya, 2015-17

Respiratory syncytial virus (RSV) circulates worldwide and is a leading cause of acute respiratory illness in young children. There is paucity of genomic data from purposively sampled populations by which to investigate evolutionary dynamics and transmission patterns of RSV. Here we present an analysis of 295 RSV group B genomes from Kilifi, coastal Kenya, sampled from individuals seeking outpatient care in 9 health facilities across a defined geographical area (890 km2), over 2 RSV epidemics between 2015 and 2017. RSVB diversity was characterized by multiple viral introductions into the area and co-circulation of distinct genetic groups or clusters, which transmitted and diversified locally but with varying frequency. Bayesian analyses indicated a strong spatially and temporally structured viral population suggesting extensive within-epidemic virus transmission. Phylogeographic analysis provided a strong support for epidemiological linkage from one central health facility to other facilities. Increase in relative diversity paralleled increase in seasonal viral incidence. Importantly, we identified a cluster of viruses (n=91) that emerged in the 2016/17 epidemic, carrying distinct amino-acid signatures including a novel non-synonymous change (K68Q) in antigenic site θ in the Fusion gene. A different non-synonymous change K68N was recently associated with escape from a potent neutralizing monoclonal antibody (MEDI8897). RSVB diversity was additionally marked by signature non-synonymous substitutions that were unique to particular genomic clusters, some of which were under diversifying selection. Our findings provide insights into recent evolutionary and epidemiologic behaviors of RSV group B, and highlight possible emergence of a novel antigenic variant, which has implications on current prophylactic development strategies.