Biomedicine & Pharmacotherapy (Aug 2024)
Preclinical in vivo assessment of the activity of AZD7442 anti-SARS-CoV-2 monoclonal antibodies against Omicron sublineages
- Jean-Sélim Driouich,
- Maxime Cochin,
- Guillaume Lingas,
- Léa Luciani,
- Cécile Baronti,
- Ornéllie Bernadin,
- Magali Gilles,
- Paola Mariela Saba Villarroel,
- Grégory Moureau,
- Paul-Rémi Petit,
- Axelle Dupont,
- Jacques Izopet,
- Nassim Kamar,
- Brigitte Autran,
- Gilles Paintaud,
- Sophie Caillard,
- Amandine le Bourgeois,
- Christophe Richez,
- Lionel Couzi,
- Aliénor Xhaard,
- Zora Marjanovic,
- Jerome Avouac,
- Caroline Jacquet,
- Dany Anglicheau,
- Morgane Cheminant,
- Stéphanie Nguyen,
- Benjamin Terrier,
- Jacques Eric Gottenberg,
- Caroline Besson,
- Sophie Letrou,
- Josephine Tine,
- Joe Miantezila Basilua,
- Denis Angoulvant,
- Coralie Tardivon,
- Gilles Blancho,
- Guillaume Martin-Blondel,
- Yazdan Yazdanpanah,
- France Mentré,
- Vincent Lévy,
- Franck Touret,
- Jérémie Guedj,
- Xavier de Lamballerie,
- Antoine Nougairède
Affiliations
- Jean-Sélim Driouich
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France; Corresponding authors.
- Maxime Cochin
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Guillaume Lingas
- Université de Paris Cité, IAME, INSERM, Paris F-75018, France
- Léa Luciani
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Cécile Baronti
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Ornéllie Bernadin
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Magali Gilles
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Paola Mariela Saba Villarroel
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Grégory Moureau
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Paul-Rémi Petit
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Axelle Dupont
- Université de Paris Cité, IAME, INSERM, Paris F-75018, France; AP-HP, Hôpital Bichat, Département d’Épidémiologie, Biostatistique et Recherche Clinique, Paris F-75018, France
- Jacques Izopet
- CHU Toulouse, Hôpital Purpan, Laboratoire de Virologie, National Reference Center for Hepatitis E, Toulouse 31300, France; Inserm UMR 1291, CNRS UMR5051, Université Toulouse III, Toulouse 31000, France
- Nassim Kamar
- Département de Néphrologie et Transplantation d'Organes, CHU Rangueil, Toulouse 31059, France
- Brigitte Autran
- Sorbonne-Université, Cimi-Paris, Inserm U1135, CNRS ERL8255, UPMC CR7, Team ''NK and T Cell Immunity, Infections and Cancer'', Paris, France
- Gilles Paintaud
- Université de Tours, EA4245 Transplantation, Immunology and Inflammation, Tours, France
- Sophie Caillard
- Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg 67000, France; Inserm UMR S1109 Labex Transplantex, Fédération de Médecine Translationnelle, Strasbourg University, Strasbourg, France
- Amandine le Bourgeois
- Service d'hématologie clinique, CHU Nantes, 1 place Alexis Ricordeau, Nantes 44000, France
- Christophe Richez
- Hôpital Pellegrin, CHU de Bordeaux, Service de Rhumatologie, Centre de référence des maladies autoimmunes systémiques rares (RESO), UMR-CNRS 5164, Université de Bordeaux, Bordeaux, France
- Lionel Couzi
- Nephrologie-Transplantation-Dialyse, CHU Bordeaux, Bordeaux, France; CNRS-UMR 5164 Immuno ConcEpT, Université de Bordeaux, Bordeaux, France
- Aliénor Xhaard
- Service d'hématologie greffe Hôpital Saint-Louis, APHP, Université de Paris Cité, Paris, France
- Zora Marjanovic
- Sorbonne University, Paris, France; Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Paris, France; INSERM, UMRs 938, Paris, France
- Jerome Avouac
- Université de Paris Service de Rhumatologie, Hôpital Cochin, AP-HP, CUP, 27 rue du Faubourg Saint-Jacques, Paris 75014, France
- Caroline Jacquet
- Service d'Hématologie, CHRU Nancy, Hôpitaux Brabois, Vandoeuvre les Nancy, France
- Dany Anglicheau
- Department of Nephrology and kidney transplantation, Necker Hospital, APHP and Université de Paris Cité, Paris, France
- Morgane Cheminant
- Clinical Hematology, Necker-Enfants Malades University Hospital, AP-HP, F-75015, Université de Paris Cité, Paris, France
- Stéphanie Nguyen
- Sorbonne université, Groupe Hospitalier Pitié-Salpêtrière APHP, Service d'Hématologie clinique, Pavillon Georges Heuyer, 47-83 boulevard de l'Hôpital, Paris Cedex 13 75651, France; Sorbonne Université, Inserm CNRS 1135 ''NK and T Cell Immunity, Virus and Cancer'', Centre d'Immunologie et des Pathologies Infectieuses (CIMI), UPMC UMRS CR7-Inserm U1135-CNRS ERL 8255, faculté de Médecine Sorbonne Université, Site Pitié-Salpêtrière, 91 boulevard de l'Hôpital, Paris 75013, France
- Benjamin Terrier
- Assistance Publique-Hôpitaux de Paris, Département de Médecine Interne, Centre de Référence National pour les maladies auto-immunes systémiques rares, Hôpital Cochin Paris, Université Paris, France
- Jacques Eric Gottenberg
- Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; CNR RESO, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France; Laboratoire d'Immunopathologie et de Chimie Thérapeutique, Institut de Biologie Moléculaire et Cellulaire (IBMC), CNRS UPR3572, Strasbourg, France
- Caroline Besson
- Université Paris-Saclay, UVSQ, CESP-INSERM1018, CH de Versailles, Le Chesnay 78150, France
- Sophie Letrou
- AP-HP, Hôpital Bichat, Département d’Épidémiologie, Biostatistique et Recherche Clinique, Paris F-75018, France
- Josephine Tine
- ANRS|Emerging Infectious Diseases, Department of Clinical Research, Paris, France
- Joe Miantezila Basilua
- ANRS|Emerging Infectious Diseases, Department of Clinical Research, Paris, France
- Denis Angoulvant
- Service de Cardiologie, CHRU de Tours & UMR Inserm 1327 ISCHEMIA ''Membrane Signaling and Inflammation in Reperfusion Injuries'', Université de Tours, Tours F37000, France
- Coralie Tardivon
- AP-HP, Hôpital Bichat, Département d’Épidémiologie, Biostatistique et Recherche Clinique, Paris F-75018, France
- Gilles Blancho
- CHU Nantes, Nantes Université, Service de Néphrologie - Immunologie Clinique, ITUN, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes F-44000, France
- Guillaume Martin-Blondel
- Service des Maladies Infectieuses et Tropicales, CHU de Toulouse & Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), INSERM UMR1291 - CNRS UMR5051 - Université Toulouse III, France
- Yazdan Yazdanpanah
- Université Paris Cité, INSERM UMRS 1137 IAME, Paris, France
- France Mentré
- Université de Paris Cité, IAME, INSERM, Paris F-75018, France; AP-HP, Hôpital Bichat, Département d’Épidémiologie, Biostatistique et Recherche Clinique, Paris F-75018, France
- Vincent Lévy
- Département de Recherche Clinique, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord and CRESS INSERM U1153, ECSTRRA Team, Paris, France
- Franck Touret
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Jérémie Guedj
- Université de Paris Cité, IAME, INSERM, Paris F-75018, France
- Xavier de Lamballerie
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France
- Antoine Nougairède
- Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), France; Corresponding authors.
- Journal volume & issue
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Vol. 177
p. 116988
Abstract
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.