Driouich J.S., Cochin M., Lingas G., Luciani L., Baronti Cécile, Bernardin O., Gilles Magali, Saba Villarroel P.M., Moureau G., Petit P.R., Dupont A., Izopet J., Kamar N., Autran B., Paintaud G., Caillard S., Le Bourgeois A., Richez C., Couzi L., Xhaard A., Marjanovic Z., Avouac J., Jacquet C., Anglicheau D., Cheminant M., Nguyen S., Terrier B., Gottenberg J.E., Besson C., Letrou S., Tine J., Miantezila Basilua J., Angoulvant D., Tardivon C., Blancho G., Martin-Blondel G., Yazdanpanah Y., Mentré F., Lévy V., Touret Franck, Guedj J., De Lamballerie X., Nougairède A. (2024). Preclinical in vivo assessment of the activity of AZD7442 anti-SARS-CoV-2 monoclonal antibodies against Omicron sublineages. Biomedicine and Pharmacotherapy, 177, 116988 [11 p.]. ISSN 0753-3322.
Titre du document
Preclinical in vivo assessment of the activity of AZD7442 anti-SARS-CoV-2 monoclonal antibodies against Omicron sublineages
Année de publication
2024
Auteurs
Driouich J.S., Cochin M., Lingas G., Luciani L., Baronti Cécile, Bernardin O., Gilles Magali, Saba Villarroel P.M., Moureau G., Petit P.R., Dupont A., Izopet J., Kamar N., Autran B., Paintaud G., Caillard S., Le Bourgeois A., Richez C., Couzi L., Xhaard A., Marjanovic Z., Avouac J., Jacquet C., Anglicheau D., Cheminant M., Nguyen S., Terrier B., Gottenberg J.E., Besson C., Letrou S., Tine J., Miantezila Basilua J., Angoulvant D., Tardivon C., Blancho G., Martin-Blondel G., Yazdanpanah Y., Mentré F., Lévy V., Touret Franck, Guedj J., De Lamballerie X., Nougairède A.
Source
Biomedicine and Pharmacotherapy, 2024,
177, 116988 [11 p.] ISSN 0753-3322
Therapeutic 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.
Plan de classement
Santé : généralités [050]
;
Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010093047]
Identifiant IRD
fdi:010093047
