Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 07 2023
19 07 2023
Historique:
received:
03
02
2023
accepted:
10
07
2023
medline:
21
7
2023
pubmed:
20
7
2023
entrez:
19
7
2023
Statut:
epublish
Résumé
Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.
Identifiants
pubmed: 37468530
doi: 10.1038/s41467-023-40057-8
pii: 10.1038/s41467-023-40057-8
pmc: PMC10356750
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
nirsevimab
VRN8S9CW5V
Recombinant Proteins
0
Banques de données
ClinicalTrials.gov
['NCT02878330', 'NCT03979313']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4347Informations de copyright
© 2023. The Author(s).
Références
J Clin Microbiol. 2020 Dec 17;59(1):
pubmed: 33087438
Pediatrics. 2013 Aug;132(2):e341-8
pubmed: 23878043
Sci Transl Med. 2017 May 3;9(388):
pubmed: 28469033
Lancet Infect Dis. 2023 Jul;23(7):856-866
pubmed: 36940703
Pediatrics. 2014 Aug;134(2):e620-38
pubmed: 25070304
PLoS One. 2016 Jun 03;11(6):e0156798
pubmed: 27258388
Nat Med. 2023 May;29(5):1172-1179
pubmed: 37095249
PLoS One. 2014 Oct 07;9(10):e109191
pubmed: 25290155
Clin Infect Dis. 2021 Dec 6;73(11):e4400-e4408
pubmed: 32897368
N Engl J Med. 2020 Jul 30;383(5):415-425
pubmed: 32726528
J Pediatric Infect Dis Soc. 2020 Nov 10;9(5):587-595
pubmed: 31868913
Pediatrics. 2020 Jul;146(1):
pubmed: 32546583
N Engl J Med. 2023 Apr 20;388(16):1533-1534
pubmed: 37018470
EBioMedicine. 2021 Nov;73:103651
pubmed: 34775220
Nucleic Acids Res. 2012 Jul;40(Web Server issue):W281-7
pubmed: 22638583
N Engl J Med. 2009 Feb 5;360(6):588-98
pubmed: 19196675
Lancet. 2022 May 28;399(10340):2047-2064
pubmed: 35598608
Lancet Child Adolesc Health. 2023 Mar;7(3):180-189
pubmed: 36634694
Virology. 2012 Dec 5;434(1):129-36
pubmed: 23062737
N Engl J Med. 2022 Mar 3;386(9):837-846
pubmed: 35235726
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
J Infect Dis. 2018 Jul 13;218(4):572-580
pubmed: 29617879
Virology. 1998 Nov 10;251(1):206-14
pubmed: 9813216
Science. 2013 May 31;340(6136):1113-7
pubmed: 23618766
Antimicrob Agents Chemother. 2017 Feb 23;61(3):
pubmed: 27956428
Pediatr Infect Dis J. 2018 Sep;37(9):886-892
pubmed: 29373476
Science. 2013 Nov 1;342(6158):592-8
pubmed: 24179220