Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study

Slim Fourati; Alawiya Reslan; Jérome Bourret; Jean-Sébastien Casalegno; Yannis Rahou; Lionel Chollet; Sylvie Pillet; Pauline Tremeaux; Nefert Candace Dossou; Elyanne Gault; Maud Salmona; Berthe-Marie Imbert-Marcille; Audrey Mirand; Sylvie Larrat; Alice Moisan; Stéphane Marot; Aurélie Schnuriger; Nicolas Veyrenche; Ilka Engelmann; Lynda Handala; Amandine Henry; Valentin Stephan; Ségolène Brichler; Véronique Avettand-Fenoel; Nael Zemali; Caroline Lefeuvre; Charlotte Pronier; Luc Deroche; Marie-Christine Jaffar-Bandjee; Lina Mouna; Catherine Francois; Alexandre Regueme; Cédric Hartard; Sylvie Rogez; Floriane Gallais; Arnaud Ly; Christophe Rodriguez; Georges dos Santos; Etienne Simon-Loriere; Olivier Schwartz; Julian Buchrieser; Jean-Miichel Pawlotsky; Frédéric Lemoine; Etienne Audureau; Marie-Anne Rameix-Welti; Naël Zemali; Sonia Burrel; Zakasoa-Mbololona Zavaoarisaina; Romain Legros; Boris Derman; Vincent Pargny; Hortense Petat; Jean-Christophe Plantier; Salim Ferrani; Jérome Guinard; Clémence Guillaume; Gilbert Mchantaf; Victoria Marie; Laurent Bret; Fabien Lesne; Anthony de Oliveira; Kazali Alidjinou; Vincent Gardan; Loic de Pontual; Camille Aupiais; Marine Perrier; Pierre Jatteau; Djeneba Fofana; Théophile Cocherie; Elisa Teyssou; Cathia Soulié; Vincent Calvez; Anne Faisant; Guillaume Mortamet; Caroline Tournegros; Mohamed Habib; Aymeric Cantais; Franck Zekre; Thomas Bourlet; Oulfa Boussetta-Charfi; Sara Chenafi-Adham; Eva Gleizes; Elise Bouthry; Fairly Warnakulasuriya; Quentin Le Hingrat; Marie-Christine Jaffar; Diana Heaugwane; Benjamin Azemar; Nicolas Mnemosyme; Laurent Souply; Sandrine Castelain; Cinthia Rames; Arnaud Bécourt; Eric Jeziorski; Vincent Foulongne; Steven Henry; Léa Domitien; Catherine Gaudy-Graffin; Agathe Crémadés; Alessandra Pennisi; Jérôme Le Goff; Sarah Mafi; Audrey Gabassi; Marie-Laure Néré; Naim Ouldali; Stéphane Bonacorsi; Senhaji Rachik Abdeljalil; Alawyia Reslan; Frédérique Lemoine; Kévin da Silva; Samar Berreira Ibraim; Emilie Yab; Vincent Enouf; Flora Donati; Matthieu Prot; Banujaa Jeyarajah; Astrid Vabret; Jean-Michel Pawlotsky; Pierre Cappy; Alexandre Soulier; Mohamed Ader; Sarah Seng; Pierre-André Natella; Laurence Fagour; Anne-Julie Schapira; Olivier Flechelles; Nicolas Leveque; Claire Morton Fauche; Louise Castain; Audreay Rodallec; Justine Sourice; Christele Gras-Le Guen; Anne Chauvire-Drouard; Frédérique Moreau; Claire Deback; Morgane Solis; Léa Pilorgé; Sophie Vallet; Léa Gaitan; Cecile Henquell; Vincent Thibault; Pauline Trémeaux; Isabelle Claudet; Mélanie Pucelle; Laetitia Staes; Camille Vellas; Romain Carcenac; Alexandre Gaymard; Jose Kombou; Antonin Bal; Stanislas Ogoudjobi

doi:10.1016/S1473-3099(24)00570-X

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Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study

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Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study

Slim Fourati, Alawiya Reslan, Jérome Bourret, Jean-Sébastien Casalegno, Yannis Rahou, Lionel Chollet, Sylvie Pillet, Pauline Tremeaux, Nefert Candace Dossou, Elyanne Gault, …

The Lancet Infectious Diseases, Vol.25(3), pp.301-311

2024

DOI: https://doi.org/10.1016/S1473-3099(24)00570-X

Abstract

BackgroundNirsevimab, a long-acting monoclonal antibody, has been approved for the prevention of respiratory syncytial virus (RSV) infection in infants. In France, more than 210 000 single doses were administered in infants younger than 1 year during the 2023–24 season. In this context, the selection and spread of escape variants might be a concern. Here, we aimed to characterise RSV associated with breakthrough infection.MethodsWe did a multicentre, national, observational study in France during the 2023–24 RSV season in RSV-infected infants (aged <1 year) who either received or did not receive a dose of nirsevimab before their first RSV season. We excluded infants with insufficient information about nirsevimab treatment or without parental consent. We used respiratory samples collected in each laboratory for full-length RSV RNA sequencing to analyse changes in the nirsevimab binding site Ø. We tested clinical RSV isolates for neutralisation by nirsevimab. We analysed F candidate substitutions by fusion-inhibition assay.FindingsOf the 695 RSV infected infants, we analysed 545 (78%) full-length RSV genome sequences: 260 (48%) from nirsevimab-treated breakthrough infections (236 [91%] RSV-A and 24 [9%] RSV-B) and 285 (52%) from untreated RSV-infected infants (236 [83%] RSV-A and 49 [17%] RSV-B). Analysis of RSV-A did not reveal any substitution in site Ø known to be associated with resistance to nirsevimab. Two (8%) of 24 RSV-B breakthrough infections had resistance-associated substitutions: F:N208D (dominant resistance-associated substitution) and a newly described F:I64M plus F:K65R combination (minority resistance-associated substitution), both of which induced high levels of resistance in the fusion-inhibition assay.InterpretationThis study is, to the best of our knowledge, the largest genotypic and phenotypic surveillance study of nirsevimab breakthrough infections to date. Nirsevimab breakthrough variants remain very rare despite the drug's widespread use. The detection of resistance-associated substitutions in the RSV-B F protein highlights the importance of active molecular surveillance.

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Title: Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study
Creators - without role: Slim Fourati - Assistance Publique – Hôpitaux de Paris
Alawiya Reslan - Inserm
Jérome Bourret - Institut Pasteur
Jean-Sébastien Casalegno - Université Claude Bernard Lyon 1
Yannis Rahou - Inserm
Lionel Chollet - Centre Hospitalier Intercommunal Toulon-La Seyne-sur-Mer
Sylvie Pillet - Hôpital Nord
Pauline Tremeaux - Virologie
Nefert Candace Dossou - Université de Caen Normandie
Elyanne Gault - Université de Versailles Saint-Quentin-en-Yvelines
Maud Salmona - Hôpital Saint-Louis
Berthe-Marie Imbert-Marcille - Centre Hospitalier Universitaire de Nantes
Audrey Mirand - Charmo University
Sylvie Larrat - Centre Hospitalier Universitaire de Grenoble
Alice Moisan - Inserm
Stéphane Marot - Sorbonne Université
Aurélie Schnuriger - Sorbonne Université
Nicolas Veyrenche - Université de Montpellier, Pathogenesis and Control of Chronic and Emerging Infections - PCCEI
Ilka Engelmann - Université de Montpellier
Lynda Handala - Centre Hospitalier Universitaire de Tours
Amandine Henry - Centre Hospitalier Victor Dupouy
Valentin Stephan - Centre Hospitalier Régional Universitaire de Brest
Ségolène Brichler - Hôpital Avicenne
Véronique Avettand-Fenoel - Institut Cochin
Nael Zemali - Centre Hospitalier Universitaire de Bordeaux
Caroline Lefeuvre - Centre Hospitalier Universitaire d'Angers
Charlotte Pronier - Centre Hospitalier Universitaire de Rennes
Luc Deroche - Pharmacologie des anti-infectieux et antibiorésistance
Marie-Christine Jaffar-Bandjee - Centre Hospitalier Universitaire de La Réunion
Lina Mouna - Assistance Publique – Hôpitaux de Paris
Catherine Francois - Université de Picardie Jules Verne
Alexandre Regueme - Centre Hospitalier Universitaire de Lille
Cédric Hartard - Université de Lorraine
Sylvie Rogez - Virologie
Floriane Gallais - Hôpitaux Universitaires de Strasbourg
Arnaud Ly - Hôpitaux Universitaires Henri-Mondor
Christophe Rodriguez - Assistance Publique – Hôpitaux de Paris
Georges dos Santos - Université de Montpellier, Pathogenesis and Control of Chronic and Emerging Infections - PCCEI
Etienne Simon-Loriere - Université Paris Cité
Olivier Schwartz - Université Paris Cité
Julian Buchrieser - Institut Pasteur
Jean-Miichel Pawlotsky - Assistance Publique – Hôpitaux de Paris
Frédéric Lemoine - Université Paris Cité
Etienne Audureau - Hôpitaux Universitaires Henri-Mondor
Marie-Anne Rameix-Welti - Infection et inflammation
Naël Zemali - Centre Hospitalier Universitaire de Bordeaux
Sonia Burrel - Laboratoire de Microbiologie Fondamentale et Pathogénicité
Alice Moisan - Inserm
Zakasoa-Mbololona Zavaoarisaina
Romain Legros - UNIROUEN - UFR Santé
Boris Derman - Virologie
Vincent Pargny - UNIROUEN - UFR Santé
Hortense Petat - Dynamique Microbienne associée aux Infections Urinaires et Respiratoires
Jean-Christophe Plantier - Dynamique Microbienne associée aux Infections Urinaires et Respiratoires
Véronique Avettand-Fenoel - Institut Cochin
Salim Ferrani
Jérome Guinard - Centre hospitalier régional d'Orléans
Clémence Guillaume - Centre de Recherches Sémiotiques
Gilbert Mchantaf
Victoria Marie
Laurent Bret
Fabien Lesne
Anthony de Oliveira
Alexandre Regueme - Centre Hospitalier Universitaire de Lille
Kazali Alidjinou
Lionel Chollet - Centre Hospitalier Intercommunal Toulon-La Seyne-sur-Mer
Vincent Gardan
Ségolène Brichler - Hôpital Avicenne
Loic de Pontual
Camille Aupiais
Stéphane Marot - Sorbonne Université
Aurélie Schnuriger - Sorbonne Université
Marine Perrier
Pierre Jatteau
Djeneba Fofana
Théophile Cocherie
Elisa Teyssou
Cathia Soulié
Vincent Calvez
Sylvie Larrat - Centre Hospitalier Universitaire de Grenoble
Anne Faisant
Guillaume Mortamet
Caroline Tournegros
Mohamed Habib
Sylvie Pillet - Hôpital Nord
Aymeric Cantais
Franck Zekre
Thomas Bourlet
Oulfa Boussetta-Charfi
Sara Chenafi-Adham
Eva Gleizes
Cédric Hartard - Université de Lorraine
Caroline Lefeuvre - Centre Hospitalier Universitaire d'Angers
Elise Bouthry
Lina Mouna - Assistance Publique – Hôpitaux de Paris
Fairly Warnakulasuriya
Quentin Le Hingrat
Marie-Christine Jaffar
Diana Heaugwane
Benjamin Azemar
Nicolas Mnemosyme
Laurent Souply
Sandrine Castelain - Centre Hospitalier Universitaire Amiens-Picardie
Cinthia Rames
Arnaud Bécourt
Ilka Engelmann - Université de Montpellier
Eric Jeziorski
Vincent Foulongne
Steven Henry
Léa Domitien
Catherine Gaudy-Graffin
Agathe Crémadés
Amandine Henry - Centre Hospitalier Victor Dupouy
Alessandra Pennisi
Maud Salmona - Hôpital Saint-Louis
Jérôme Le Goff
Sarah Mafi
Audrey Gabassi
Marie-Laure Néré
Naim Ouldali
Stéphane Bonacorsi
Marie-Anne Rameix-Welti
Senhaji Rachik Abdeljalil
Alawyia Reslan
Yannis Rahou - Inserm
Jérome Bourret - Institut Pasteur
Frédérique Lemoine
Kévin da Silva
Samar Berreira Ibraim
Emilie Yab
Vincent Enouf
Flora Donati
Matthieu Prot
Banujaa Jeyarajah
Etienne Simon-Loriere - Université Paris Cité
Nefert Candace Dossou - Université de Caen Normandie
Astrid Vabret
Slim Fourati - Assistance Publique – Hôpitaux de Paris
Christophe Rodriguez - Assistance Publique – Hôpitaux de Paris
Jean-Michel Pawlotsky
Pierre Cappy
Alexandre Soulier
Mohamed Ader
Sarah Seng
Arnaud Ly - Hôpitaux Universitaires Henri-Mondor
Pierre-André Natella
Etienne Audureau - Hôpitaux Universitaires Henri-Mondor
Georges dos Santos - Centre Hospitalier Universitaire de Martinique
Laurence Fagour
Anne-Julie Schapira
Olivier Flechelles
Luc Deroche
Nicolas Leveque
Claire Morton Fauche
Berthe-Marie Imbert-Marcille - Centre Hospitalier Universitaire de Nantes
Louise Castain
Audreay Rodallec
Justine Sourice
Christele Gras-Le Guen
Anne Chauvire-Drouard
Elyanne Gault - Université de Versailles Saint-Quentin-en-Yvelines
Frédérique Moreau
Claire Deback
Floriane Gallais
Morgane Solis
Valentin Stephan - Centre Hospitalier Régional Universitaire de Brest
Léa Pilorgé
Sophie Vallet
Léa Gaitan
Sylvie Rogez
Audrey Mirand
Cecile Henquell
Charlotte Pronier - Centre Hospitalier Universitaire de Rennes
Vincent Thibault - Bacterial RNAs & Medicine
Pauline Trémeaux
Isabelle Claudet
Mélanie Pucelle
Laetitia Staes
Camille Vellas
Romain Carcenac
Nicolas Veyrenche - Hôpital Necker-Enfants Malades
Jean-Sébastien Casalegno
Alexandre Gaymard
Jose Kombou
Antonin Bal
Stanislas Ogoudjobi
Publication Details: The Lancet Infectious Diseases, Vol.25(3), pp.301-311
Grant note: ANRS Maladies Infectieuses Emergentes and the French Ministry of Health and Prevention
Identifiers: 9933831309311
Academic Unit: Pathogenesis and Control of Chronic and Emerging Infections - PCCEI
Language: English
Resource Type: Journal article
Local Fields: hal-04743079