Complement augments antibody neutralization of SARS-CoV-2 variants
Year: 2026
Type: article
Abstract: 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.
Source: Science Translational Medicine
Authors: Martin Jungbauer-Groznica, Pierre Rosenbaum, Isabelle Staropoli, Florence Guivel-Benhassine, Pierre-Henri Commere, Tom Perisse, Lily Bruyère, Aura Fantin Rengifo, Alejandro De Cruz, Andrea Cottignies-Calamarte, Sabina Andreu, Laurent Hocqueloux, Thierry 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, Lucile Picard, Nicolas Mongardon, Alexandre Soulier, Melissa N'debi, Sarah Seng, Mohamed Ader, Pierre Cappy, Christophe Rodriguez, Jean-Michel Pawlotsky, Etienne Audureau, Pierre-Andre Natella, Frederic Pene, Anne-Sophie L'honneur, Adrien Joseph, Elie Azoulay, Megan Fraisse, Maud Salmona, Marie-Laure Chaix, Charles-Edouard Luyt, David Levy, Julien Mayaux, Stephane Marot, Juliette Bernier, Vincent Bonny, Tomas Urbina, Hafid Ait-Oufella, Eric Maury, Laurence Morand-Joubert, Djeneba Bocar Fofana, Jean-Francois Timsit, Diane Descamps, Quentin Le Hingrat, Guillaume Voiriot, Nina De Montmollin, Mathieu Turpin, Stéphane Gaudry, Ségolène Brichler, Fabrice Uhel, Damien Roux, Luce Landraud, Anne-Claire Maherault, Tài Olivier Pham, Amal Chaghouri, Anne-Marie Roque-Alfonso, Nicholas Heming, Djillali Annane, Marie-Alice Bovy, Sylvie Meireles, Antoine Vieillard-Baron, Elyanne Gault, Sébastien Jochmans, Aurélia Pitsch, Guillaume Chevrel, Céline Clergue, Kubab Sabah, Damien Contou, Amandine Henry, Malo Emery, Claudio Garcia-Sanchez, Ferhat Meziani, Louis-Marie Jandeaux, Samira Fafi-Kremer, Elodie Laugel, Sébastien Preau, Raphaël Favory, Claire Bourel, Côme Bureau, Estelle Danche, Alexandre Gaudet, Geoffrey Ledoux, Aurélie Guigon, Antoine Kimmoun, Evelyne Schvoerer, Cédric Hartard, Charles Damoisel, Anne-Marie Roque-Alfonso, Nicolas Brechot, Hélène Péré, Antoine Guillon, Lynda Handala, François Beloncle, Achille Kouachet, Mathilde Taillantou-Candau, Caroline Lefeuvre, Alexandra Ducancelle, Rémi Coudroy, Arnaud W. Thille, François Arrive, Sylvain Le Pape, Laura Marchasson, Luc Deroche, Nicolas Leveque, Jean-Marc Tadié, Valentin Coirier, Vincent Thibault, Claire Grolhier, Béatrice La Combe, Séverine Haouisee, Alexandre Boyer, Sonia Burrel, Fabienne Tamion, Gaetan Beduneau, Christophe Girault, Maximillien Grall, Dorothée Carpentier, Alice Moisan, Elodie 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, Raphaele Germi, Aurelie Truffot, Guillaume Thiery, Sylvie Pillet, Kada Klouche, Ilka Engelmann, Edouard Tuaillon, Cécile Aubron, Adissa Tran, Sophie Vallet, Pierre-Emmanuel Charles, Alexis De Rougemont, Bertrand Souweine, Cecile Henquell, Audrey Mirand, Bruno Mourvillier, Laurent Andreoletti, 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 Stephan, Guillaume Louis, Christelle Jost, Pascale Perez, Sébastien Gibot, Evelyne Schvoerer, François Barbier, Jerome Guinard, Véronique Avettand-Fenoel, 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
Institutions: Institut Pasteur, Université Paris Cité, Lyon 1 Université, Centre National de la Recherche Scientifique, Inserm, Hospices Civils de Lyon, Centre International de Recherche en Infectiologie, Universidad Autónoma de Madrid, Université d'Orléans, Centre hospitalier universitaire d'Orléans, Laboratoire Interdisciplinaire pour l’Innovation et la Recherche en Santé d’Orléans, Université Paris-Est Créteil, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique – Hôpitaux de Paris, Department of Virology, Hôpitaux Universitaires Henri-Mondor, Institut Mondor de Recherche Biomédicale, Centre Hospitalier Universitaire de Saint-Étienne, Université Jean Monnet, Institut de Recherche Vaccinale
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7170065724