2026article
Complement augments antibody neutralization of SARS-CoV-2 variants
Martin Groznica, Pierre Rosenbaum, Isabelle Staropoli, Florence Guivel‐Benhassine, Pierre‐Henri Commère, Tom Perisse, Lily Bruyère, Aura Fantin Rengifo, Alejandro De Cruz, Andréa Cottignies-Calamarte, Sabina Andreu, Laurent Hocqueloux, T Prazuck, Cyril Planchais, Michael White, Sophie Novault, Sophie Trouillet‐Assant, SEVARVIR investigators, Slim Fourati, Nicolas de Prost, Martin Killian, Stéphane Paul, Olivier Schwartz, Hugo Mouquet, Timothée Bruel, Pierre Bay, Keyvan Razazi, Armand Mekontso Dessap, L Picard, Nicolas Mongardon, Alexandre Soulier, Mélissa N’Debi, Sarah Seng, Mohamed Ader, Pierre Cappy, Christophe Rodriguez, Jean-Michel Pawlotsky, Étienne Audureau, Pierre-André Natella, Frédéric Pène, Anne-Sophie L'honneur, Adrien Joseph, Elie Azoulay, Megan Fraissé, Maud Salmona, Marie‐Laure Chaix, Charles‐Édouard Luyt, David Levy, Julien Mayaux, Stephane Marot, J J Bernier, Vincent Bonny, Tomas Urbina, Hafid Ait‐Oufella, Eric Maury, Laurence Morand-Joubert, D Fofana, Jean-François Timsit, Diane Descamps, Quentin Le Hingrat, Guillaume Voiriot, Nina de Montmollin, Mathieu turpin, Stéphane Gaudry, Ségolène Brichler, Fabrice Uhel, Damien Roux, Luce Landraud, A.-C. Maherault, Tai Olivier Pham, Amal Chaghouri, Anne-Marie Roque-Alfonso, Nicholas Heming, Djillali Annane, Marie-Alice Bovy, Sylvie Meireles, Antoine Vieillard-Baron, Elyanne Gault, Sébastien Jochmans, A. Pitsch, Guillaume Chevrel, Céline Clergue, Kubab Sabah, Damien Contou, Amandine Henry, Malo Emery, Claudio Garcia-Sanchez, Ferhat Meziani, Louis-Marie Jandeaux, S. Fafi-Kremer, Elodie Laugel, Sébastien Preau, Raphaël Favory, Claire Bourel, Côme Bureau, Estelle Danche, Alexandre Gaudet, G. Ledoux, Aurélie Guigon, Antoine Kimmoun, Evelyne Schvoerer, Cédric Hartard, Charles Damoisel, Nicolas Bréchot, Hélène Péré, Antoine Guillon, Lynda Handala, François Beloncle, Achille Kouachet, Mathilde Taillantou-Candau, Caroline Lefeuvre, Alexandra Ducancelle, Rémi Coudroy, Arnaud W. Thille, François Arrivé, Sylvain Le Pape, Laura Marchasson, Luc Deroche, Nicolas Lévêque, Jean-Marc Tadié, Valentin Coirier, Vincent Thibault, Claire Grolhier, Béatrice La Combe, Séverine Haouisee, Alexandre Boyer, Sonia Burrel, Fabienne Tamion, G. Béduneau, Christophe Girault, Maximillien Grall, Dorothée Carpentier, Alice Moisan, Élodie Alessandri-Gradt, Véronique Lemee, Adeline Baron, Marie Gueudin, Emmanuel Canet, Audrey Rodallec, Berthe Marie Imbert, Clément Saccheri, Géraldine Gonfrier, Sami Hraeich, Pierre-Edouard Fournier, Philippe Colson, Cédric Darreau, Jean Thomin, Anaïs Dartevel, Sylvie Larrat, Raphaële Germi, Aurélie Truffot, Guillaume Thiery, Sylvie Pillet, Kada Klouche, Ilka Engelmann, Édouard Tuaillon, Cécile Aubron, Adissa Tran, Sophie Vallet, Pierre-Emmanuel Charles, Alexis de Rougemont, Bertrand Souweine, Cecile Henquell, Audrey Mirand, B Mourvillier, Laurent Andréoletti, Quentin Lecomte-Thenot, Damien du Cheyron, Nefert Candace Dossou, Astrid Vabret, Gaël Piton, Jean-Christophe Navellou, Quentin Lepiller, Thomas DAIX, Sébastien Hantz, Sylvie Roger, Benjamine Sarton, Camille Vellas, Claire Roger, Robin Stéphan, Guillaume Louis, Christelle Jost, P. de Unamuno Pérez, Sébastien Gibot, François Barbier, Jerome Guinard, Véronique Avettand-Fènoël, Jean‐Philippe Rigaud, Elodie Blondel, Amélie Renou, Laurent Souply, Hossein Mehdoui, Laurence Fagour, Hugues Georges, Pierre Patoz, Asaël Berger, Julien Exinger, Jean-Christophe Richard, Alexandre Gaymard, François Danion, Manuel Etienne, Anne-Laure Mounayar, Matthieu Buscot, David Luque-Paz, Paul Loubet, Romaric Larcher, Myriam Chiaruzzi, Aurélie Martin, Marie Poupard, Fanny Villa, Guillaume Martin-Blondel, Florence Ader, Emmanuel Faure, Giovanna Melica, Nathan Peiffer-Smadja, Aurélien Dinh, Karine Lacombe
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Résumé fourni par la source
The complement system is a major effector system of the humoral immune response, but its capacity to cooperate with antibodies to inhibit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a host remains poorly characterized. Here, we combined authentic virus neutralization, antibody engineering, and single viral particle analysis by flow virometry to show that complement enhances antibody neutralization of SARS-CoV-2. Addition of complement increased neutralization titers of sera from convalescent individuals ( n = 14), vaccinated individuals ( n = 15), and individuals with hybrid immunity ( n = 15) against D614G, BA.1, XBB.1.5, and JN.1 variants by up to 42-fold. D614G and BA.1 displayed a high level of neutralization, which was only slightly improved by adding complement. Conversely, neutralization of XBB.1.5 and JN.1 was weak but strongly enhanced by complement. Among the 32 JN.1 nonneutralizers, 22 regained detectable neutralization in the presence of complement. The enhancement mainly relied on cross-reactive anti-S2 antibodies, but monoclonal antibodies targeting the receptor binding domain and N-terminal domain could also be augmented. Viral inhibition required antibody Fc hexamerization, C1q recruitment, and C3 deposition, but it was independent of the membrane attack complex formed by C9. Consistently, complement components were deposited at the surfaces of viral particles with no detectable virolysis. In sera from individuals with severe COVID-19, both complement-mediated neutralization and anti-S2 antibody levels were associated with improved survival. Overall, our data show that complement potentiates the ability of antispike antibodies to neutralize immune-evasive SARS-CoV-2 variants.
Sujets associés
SARS-CoV-2 and COVID-19 ResearchComplement system in diseasesCOVID-19 Clinical Research Studies