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Journal Article Ppublish 5 citations

PubMed: 38240255 DOI: 10.1080/22221751.2024.2307510

Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants.

Emerg Microbes Infect 13(1):2307510

Authors: Frédéric Coutant, Franck Touret, Jean-Jacques Pin, Marina Alonzo, Cécile Baronti, Sandie Munier, Mikaël Attia, Xavier de Lamballerie, Tristan Ferry, Pierre Miossec

Affiliations

  • Immunogenomics and Inflammation Research Team, University of Lyon, Edouard Herriot Hospital, Lyon, France.
  • Immunology Department, Lyon-Sud Hospital, Hospices Civils of Lyon, Pierre-Bénite, France.
  • Unité des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207), Marseille, France.
  • Eurobio Scientific/Dendritics - Edouard Herriot Hospital, Lyon, France.
  • Institut Pasteur, Université Paris Cité, CNRS UMR3569, Molecular Genetics of RNA Viruses Unit, Paris, France.
  • Department of Infectious and Tropical Diseases, Hospices Civils of Lyon - Croix-Rousse Hospital, Lyon, France.
  • CIRI, Inserm U1111, CNRS, UMR5308, ENS Lyon, Université Claude Bernard Lyon I, Lyon, France.
  • Department of Immunology and Rheumatology, Edouard Herriot Hospital, Lyon, France.

Abstract

Serological studies of COVID-19 convalescent patients have identified polyclonal lineage-specific and cross-reactive antibodies (Abs), with varying effector functions against virus variants. Individual specificities of anti-SARS-CoV-2 Abs and their impact on infectivity by other variants have been little investigated to date. Here, we dissected at a monoclonal level neutralizing and enhancing Abs elicited by early variants and how they affect infectivity of emerging variants. B cells from 13 convalescent patients originally infected by D614G or Alpha variants were immortalized to isolate 445 naturally-produced anti-SARS-CoV-2 Abs. Monoclonal antibodies (mAbs) were tested for their abilities to impact the cytopathic effect of D614G, Delta, and Omicron (BA.1) variants. Ninety-eight exhibited robust neutralization against at least one of the three variant types, while 309 showed minimal or no impact on infectivity. Thirty-eight mAbs enhanced infectivity of SARS-CoV-2. Infection with D614G/Alpha variants generated variant-specific (65 neutralizing Abs, 35 enhancing Abs) and cross-reactive (18 neutralizing Abs, 3 enhancing Abs) mAbs. Interestingly, among the neutralizing mAbs with cross-reactivity restricted to two of the three variants tested, none demonstrated specific neutralization of the Delta and Omicron variants. In contrast, cross-reactive mAbs enhancing infectivity ( = 3) were found exclusively specific to Delta and Omicron variants. Notably, two mAbs that amplified the cytopathic effect of the Delta variant also exhibited neutralization against Omicron. These findings shed light on functional diversity of cross-reactive Abs generated during SARS-CoV-2 infection and illustrate how the balance between neutralizing and enhancing Abs facilitate variant emergence.

MeSH

Infections, Antibodies, Monoclonal, B-Lymphocytes, Communicable Diseases, Emerging, Sars Virus, Antibody-Dependent Enhancement, Covid-19, Sars-Cov-2

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