Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus
RESCEU Investigators
(2021) Nature Communications, volume 12, issue 1, pp. 1 - 11
(Article)
Abstract
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017–2020. RSV-B had lower consensus diversity than RSV-A at
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the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.
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Keywords: Aged, Antigenic Variation, Female, Genetic Variation, Humans, Infant, Male, Mutation, Missense, Respiratory Syncytial Virus Infections/immunology, Respiratory Syncytial Virus, Human/classification, Viral Proteins/genetics, Virus Replication, General Physics and Astronomy, General Chemistry, General Biochemistry,Genetics and Molecular Biology, Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Funding Information: S.B.D. has been an investigator for clinical trials of vaccines and antimicrobials for pharmaceutical companies including AstraZeneca, Merck and Janssen, and sits on an RSV advisory board for Sanofi Pastuer. M.A.A. is supported by a Sir Henry Dale Fellowship jointly funded by the Royal Society and Wellcome Trust (220171/Z/20/Z). D.Ö. and J.A. are employees of Janssen Pharmaceutica NV. F.M.-T. has received honoraria from GSK, Pfizer Inc., Sanofi Pasteur, MSD, Seqirus and Janssen for taking part in advisory boards and expert meetings and for acting as a speaker in congresses outside the scope of the submitted work. F.M.-T. has also acted as principal investigator in randomised controlled trials of the above-mentioned companies as well as Ablynx, Regeneron, Roche, Abbott, Novavax and MedImmune, with honoraria paid to his institution. F.M.-T. receives support for his research activities from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): Fondo de Investigación Sanitaria (FIS;PI1601569/PI1901090) del plan nacional de I+D+I and ‘fondos FEDER’. A.J.P. is a National Institute for Health Research (NIHR) Senior Investigator with funding from the British Research Council. The remaining authors declare no competing interests. The views expressed in this article are those of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the organisations with which the authors are employed/affiliated. Funding Information: This work was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, the NIHR Thames Valley and South Midlands Clinical Research Network, the British Research Council, and the REspiratory Syncytial virus Consortium in EUrope (RESCEU) project. RESCEU has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (grant number 116019). This Joint Undertaking receives support from the European Union Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations. Publisher Copyright: © 2021, The Author(s).
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