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Published on: April 4, 2019
Global Molecular Epidemiology of Respiratory Syncytial Virus from the 2017-2018 INFORM-RSV Study
David E Tabor1, Fiona Fernandes2, Annefleur C Langedijk3
1Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Insights
Global molecular epidemiology of Respiratory Syncytial Virus (RSV) was studied in children under 5. The pilot season found RSV B predominated globally, with genetic variations impacting potential vaccine and MAb effectiveness.
Area of Science:
- Virology
- Epidemiology
- Molecular Biology
Background:
- Respiratory Syncytial Virus (RSV) causes significant lower respiratory tract infections in young children globally.
- Annual epidemics of RSV necessitate continuous monitoring of circulating strains and their evolution.
Purpose of the Study:
- To describe the global molecular epidemiology of RSV in children under 5.
- To monitor temporal and geographical evolution of RSV strains, F protein antigenic sites, and their relation to clinical features.
- To establish a baseline for tracking new strains and potential immune escape variants.
Main Methods:
- The INFORM-RSV pilot season (2017-2018) collected 476 RSV-positive nasal samples from 8 countries.
- 410 RSV G-F gene sequences were analyzed to determine strain distribution and genetic variability.
- Sequences were compared to 2013 reference strains to identify variations in F protein antigenic sites.
Main Results:
- RSV B (BA9 genotype) predominated globally (69.0%) over RSV A (ON1 genotype) (31.0%), except in South Africa.
- Geographic clustering indicated widespread transmission and ongoing viral evolution.
- Variations in F protein antigenic sites were observed, particularly in RSV B strains at sites Ø and V.
Conclusions:
- The 2017-2018 pilot season provides a crucial molecular baseline for RSV epidemiology.
- Ongoing monitoring is essential to track emerging strains and potential neutralization escape variants.
- Findings will inform the development and effectiveness assessment of RSV vaccines and monoclonal antibodies.
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.
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