TY - JOUR
T1 - Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus
AU - Lin, Gu Lung
AU - Drysdale, Simon B.
AU - Snape, Matthew D.
AU - O’Connor, Daniel
AU - Brown, Anthony
AU - MacIntyre-Cockett, George
AU - Mellado-Gomez, Esther
AU - de Cesare, Mariateresa
AU - Bonsall, David
AU - Ansari, M. Azim
AU - Öner, Deniz
AU - Aerssens, Jeroen
AU - Butler, Christopher
AU - Bont, Louis
AU - Openshaw, Peter
AU - Martinón-Torres, Federico
AU - Nair, Harish
AU - Bowden, Rory
AU - Campbell, Harry
AU - Cunningham, Steve
AU - Bogaert, Debby
AU - Beutels, Philippe
AU - Wildenbeest, Joanne
AU - Clutterbuck, Elizabeth
AU - McGinley, Joseph
AU - Thwaites, Ryan
AU - Wiseman, Dexter
AU - Gómez-Carballa, Alberto
AU - Rodriguez-Tenreiro, Carmen
AU - Rivero-Calle, Irene
AU - Dacosta-Urbieta, Ana
AU - Heikkinen, Terho
AU - Meijer, Adam
AU - Fischer, Thea Kølsen
AU - van den Berge, Maarten
AU - Giaquinto, Carlo
AU - Abram, Michael
AU - Dormitzer, Philip
AU - Stoszek, Sonia
AU - Gallichan, Scott
AU - Rosen, Brian
AU - Molero, Eva
AU - Machin, Nuria
AU - Spadetto, Martina
AU - Golubchik, Tanya
AU - Pollard, Andrew J.
N1 - 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).
PY - 2021/12
Y1 - 2021/12
N2 - 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 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.
AB - 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 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.
KW - Aged
KW - Antigenic Variation
KW - Female
KW - Genetic Variation
KW - Humans
KW - Infant
KW - Male
KW - Mutation, Missense
KW - Respiratory Syncytial Virus Infections/immunology
KW - Respiratory Syncytial Virus, Human/classification
KW - Viral Proteins/genetics
KW - Virus Replication
UR - http://www.scopus.com/inward/record.url?scp=85113609359&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-25265-4
DO - 10.1038/s41467-021-25265-4
M3 - Article
C2 - 34446722
SN - 2041-1723
VL - 12
SP - 1
EP - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5125
ER -