Abstract
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. INFORM-RSV is a multiyear clinical study designed to describe the global molecular epidemiology of RSV in children under 5 years of age by monitoring temporal and geographical evolution of current circulating RSV strains, F protein antigenic sites, and their relationships with clinical features of RSV disease. During the pilot season (2017-2018), 410 RSV G-F gene sequences were obtained from 476 RSV-positive nasal samples collected from 8 countries (United Kingdom, Spain, The Netherlands, Finland, Japan, Brazil, South Africa, and Australia). RSV B (all BA9 genotype) predominated over RSV A (all ON1 genotype) globally (69.0% versus 31.0%) and in all countries except South Africa. Geographic clustering patterns highlighted wide transmission and continued evolution with viral spread. Most RSV strains were from infants of <1 year of age (81.2%), males (56.3%), and patients hospitalized for >24 h (70.5%), with no differences in subtype distribution. Compared to 2013 reference sequences, variations at F protein antigenic sites were observed for both RSV A and B strains, with high-frequency polymorphisms at antigenic site Ø (I206M/Q209R) and site V (L172Q/S173L/K191R) in RSV B strains. The INFORM-RSV 2017-2018 pilot season establishes an important molecular baseline of RSV strain distribution and sequence variability with which to track the emergence of new strains and provide an early warning system of neutralization escape variants that may impact transmission or the effectiveness of vaccines and MAbs under development.
Highlights
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide
INFORM-RSV is a prospective, multicenter, global molecular epidemiology study to investigate temporal and geographic diversity of RSV isolates collected from children less than 5 years of age who are admitted to the hospital or visiting the outpatient clinic and are not using preventive or treatment medication for RSV
Among the RSV-positive detections, 476 (25.9%) nasal samples were collected for inclusion in the INFORM-RSV study
Summary
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. The INFORM-RSV 2017–2018 pilot season establishes an important molecular baseline of RSV strain distribution and sequence variability with which to track the emergence of new strains and provide an early warning system of neutralization escape variants that may impact transmission or the effectiveness of vaccines and MAbs under development. Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) among infants and young children worldwide [1, 2]. Because there is no approved RSV prophylaxis for the broader population of healthy infants, more than 20 vaccine candidates and monoclonal antibodies (MAbs) are currently in clinical development [8]. Six antigenic sites (Ø and I to V) have been identified in prefusion and/or postfusion F proteins [13] with target epitopes for prophylactic neutralizing MAbs, including: palivizumab (site II), nirsevimab (site Ø), suptavumab (site V), and MK-1654 (site IV) [14]
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