An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus

By E. Traggiai, S. Becker, K. Subbarao, L. Kolesnikova, Y. Uematsu, M. Gismondo, B. Murphy, R. Rappuoli, A. Lanzavecchia. 2004

728 citations recorded by the source corpus.

Passive serotherapy can confer immediate protection against microbial infection, but methods to rapidly generate human neutralizing monoclonal antibodies are not yet available. We have developed an improved method for Epstein-Barr virus transformation of human B cells. We used this method to analyze the memory repertoire of a patient who recovered from severe acute respiratory syndrome coronavirus (SARS-CoV) infection and to isolate monoclonal antibodies specific for different viral proteins, including 35 antibodies with in vitro neutralizing activity ranging from 10−8M to 10−11M. One such antibody confers protection in vivo in a mouse model of SARS-CoV infection. These results show that it is possible to interrogate the memory repertoire of immune donors to rapidly and efficiently isolate neutralizing antibodies that have been selected in the course of natural infection.

Subfields: Immunology, Infectious Diseases, Molecular Biology

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Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “We previously characterized potent human neutralizing Abs from rare memory B cells of individuals infected with SARS-CoV (Rockx et al., 2008; Traggiai et al., 2004) or MERS-CoV (Corti et al., 2015) in complex with their respective S glycoproteins to provide molecular-level information on the…”
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, neutral): “…human monoclonal Abs (mAbs) protected animals challenged with SARS-CoV-2 (Alsoussi et al., 2020; Wu et al., 2020), various SARS-CoV isolates (Menachery et al., 2016; Rockx et al., 2008; Traggiai et al., 2004), and MERS-CoV (Corti et al., 2015; de Wit et al., 2019; Johnson et al., 2016).”
Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual (2020, background): “Potent anti-SARS-CoV neutralizing monoclonal antibodies that bind RBD are derived from different VH genes (VH1-18, VH1-69, or VH3-30) than CV30 (Prabakaran et al., 2006; Sui et al., 2004; Traggiai et al., 2004; Walls et al., 2019).”
Therapeutic potential of Toll-like receptor 9 activation (2006, background): “The B-cell-stimulatory effect of TLR9 is so great that the efficiency of hybridoma generation from purified primary human memory B cells is improved from 1–2% without CpG to 30–100% with the addition of a CpG OD”
Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus (2005, background): “The protective efficacy of several human monoclonal SARS-CoV-neutralizing antibodies has been recently demonstrated using various animal models (mice and ferrets) (118, 297, 308, 314).”
Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission (2009, background): “Multiple neutralizing epitopes have been identified, and the majority of these residues lie within the RBD, specifically within the RBD-ACE2 interface (114, 128, 136, 162).”
Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge (2008, neutral): “Several studies have shown that the generation of neutralizing antibodies against SARS-CoV is a major component of protective immunity (47, 48).”
Mining human antibody repertoires (2010, background): “In this manner, mAbs potently neutralizing the SARS corona virus or the H5N1 Influenza A virus were isolated.(51,52) Strategies allowing the long-term growth and cloning of human B cells, without immortalization by transformation with a virus or an oncogene, have also been explored.”
Immunology of COVID-19: Current State of the Science (2020, neutral): “B cells decreased progressively about 90% from 2 to 8 months after infection (Traggiai et al., 2004).”
The spike protein of SARS-CoV — a target for vaccine and therapeutic development (2009, background): “A range of neutralizing human mAbs have been generated from B cells of patients infected with SARS-Co”
COVID-19: what has been learned and to be learned about the novel coronavirus disease (2020, background): “The humoral immunity including complements such as C3a and C5a and antibodies is also essential in combating the viral infection [30,31].”
From SARS to MERS, Thrusting Coronaviruses into the Spotlight (2019, methodology): “Mice could therefore be used as a stable and reproducible animal model for the evaluation of vaccines, immune-prophylaxis, and antiviral drugs against SARS-CoV [81, 96, 109, 124, 149, [162] [163] [164] [165] [166] .”