Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies

Jérémy Dufloo (1, 2) , Ludivine Grzelak (1, 2) , Isabelle Staropoli (1) , Yoann Madec (3) , Laura Tondeur (3) , François Anna (4) , Stéphane Pelleau (5) , Aurélie Wiedemann (6) , Cyril Planchais (7) , Julian Buchrieser (1) , Rémy Robinot (1) , Marie-Noelle Ungeheuer (8) , Hugo Mouquet (7) , Pierre Charneau (4, 9) , Michael White (5) , Yves Lévy (6) , Bruno Hoen (10) , Arnaud Fontanet (3, 11) , Olivier Schwartz (1, 6) , Timothée Bruel (1, 6)

1 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
2 USPC - Université Sorbonne Paris Cité
3 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
4 Laboratoire commun Pasteur-TheraVectys
5 Malaria : parasites et hôtes - Malaria : parasites and hosts
6 VRI - Vaccine Research Institute
7 Immunologie humorale - Humoral Immunology
8 ICAReB - Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources
9 Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology
10 Direction de la recherche médicale de l'Institut Pasteur
11 CNAM - Conservatoire National des Arts et Métiers [CNAM]

Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and 21 hospitalized patients with COVID-19. We measure anti-spike immunoglobulin G (IgG), IgA, and IgM levels with the S-Flow assay and map IgG-targeted epitopes with a Luminex assay. We also evaluate neutralization, complement deposition, and antibody-dependent cellular cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC, and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than they are in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.

Keywords: ADCC; SARS-CoV-2; antibody; asymptomatic; complement

Domains: Life Sciences [q-bio]

Jérémy Dufloo, Ludivine Grzelak, Isabelle Staropoli, Yoann Madec, Laura Tondeur, et al.. Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies. Cell Reports Medicine, 2021, 2 (5), pp.100275. ⟨10.1016/j.xcrm.2021.100275⟩. ⟨pasteur-03229805⟩