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Preclinical in vivo assessment of the activity of AZD7442 anti-SARS-CoV-2 monoclonal antibodies against Omicron sublineages

dc.rights.licenseopenen_US
dc.contributor.authorDRIOUICH, Jean-Sélim
dc.contributor.authorCOCHIN, Maxime
dc.contributor.authorLINGAS, Guillaume
dc.contributor.authorLUCIANI, Léa
dc.contributor.authorBARONTI, Cécile
dc.contributor.authorBERNADIN, Ornéllie
dc.contributor.authorGILLES, Magali
dc.contributor.authorVILLARROEL, Paola Mariela Saba
dc.contributor.authorMOUREAU, Grégory
dc.contributor.authorPETIT, Paul-Rémi
dc.contributor.authorDUPONT, Axelle
dc.contributor.authorIZOPET, Jacques
dc.contributor.authorKAMAR, Nassim
dc.contributor.authorAUTRAN, Brigitte
dc.contributor.authorPAINTAUD, Gilles
dc.contributor.authorCAILLARD, Sophie
dc.contributor.authorLE BOURGEOIS, Amandine
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorRICHEZ, Christophe
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorCOUZI, Lionel
dc.contributor.authorXHAARD, Aliénor
dc.contributor.authorMARJANOVIC, Zora
dc.contributor.authorAVOUAC, Jerome
dc.contributor.authorJACQUET, Caroline
dc.contributor.authorANGLICHEAU, Dany
dc.contributor.authorCHEMINANT, Morgane
dc.contributor.authorNGUYEN, Stéphanie
dc.contributor.authorTERRIER, Benjamin
dc.contributor.authorGOTTENBERG, Jacques Eric
dc.contributor.authorBESSON, Caroline
dc.contributor.authorLETROU, Sophie
dc.contributor.authorTINE, Josephine
dc.contributor.authorBASILUA, Joe Miantezila
dc.contributor.authorANGOULVANT, Denis
dc.contributor.authorTARDIVON, Coralie
dc.contributor.authorBLANCHO, Gilles
dc.contributor.authorMARTIN-BLONDEL, Guillaume
dc.contributor.authorYAZDANPANAH, Yazdan
dc.contributor.authorMENTRÉ, France
dc.contributor.authorLÉVY, Vincent
dc.contributor.authorTOURET, Franck
dc.contributor.authorGUEDJ, Jérémie
dc.contributor.authorDE LAMBALLERIE, Xavier
dc.contributor.authorNOUGAIRÈDE, Antoine
dc.date.accessioned2024-10-15T09:53:23Z
dc.date.available2024-10-15T09:53:23Z
dc.date.issued2024-08
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/202504
dc.description.abstractEnTherapeutic monoclonal antibodies have been successful in protecting vulnerable populations against SARS-CoV-2. However, their effectiveness has been hampered by the emergence of new variants. To adapt the therapeutic landscape, health authorities have based their recommendations mostly on in vitro neutralization tests. However, these do not provide a reliable understanding of the changes in the dose-effect relationship and how they may translate into clinical efficacy. Taking the example of EvusheldTM (AZD7442), we aimed to investigate how in vivo data can provide critical quantitative results and project clinical effectiveness. We used the Golden Syrian hamster model to estimate 90 % effective concentrations (EC90) of AZD7442 in vivo against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5 variants. While our in vivo results confirmed the partial loss of AZD7442 activity for BA.1 and BA.2, they showed a much greater loss of efficacy against BA.5 than that obtained in vitro. We analyzed in vivo EC90s in perspective with antibody levels measured in a cohort of immunocompromised patients who received 300 mg of AZD7442. We found that a substantial proportion of patients had serum levels of anti-SARS-CoV-2 spike protein IgG above the estimated in vivo EC90 for BA.1 and BA.2 (21 % and 92 % after 1 month, respectively), but not for BA.5. These findings suggest that AZD7442 is likely to retain clinical efficacy against BA.2 and BA.1, but not against BA.5. Overall, the present study illustrates the importance of complementing in vitro investigations by preclinical studies in animal models to help predict the efficacy of monoclonal antibodies in humans.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.subject.enPreclinical animal model
dc.subject.enMonoclonal antibody
dc.subject.enSARS-CoV-2
dc.subject.enOmicron sublineages
dc.subject.enAZD7442
dc.subject.enClinical therapeutics
dc.title.enPreclinical in vivo assessment of the activity of AZD7442 anti-SARS-CoV-2 monoclonal antibodies against Omicron sublineages
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.biopha.2024.116988en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologieen_US
dc.identifier.pubmed38897157en_US
bordeaux.journalBiomedicine and Pharmacotherapyen_US
bordeaux.page116988en_US
bordeaux.volume177en_US
bordeaux.hal.laboratoriesImmunoConcEpT - UMR 5164en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
dc.rights.ccCC BY-NCen_US
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