Potent human neutralizing antibodies elicited by SARS-CoV-2 infection
Authors: Bin Ju et al. Link to paper: https://i.org/10.1101/2020.03.21.990770
Journal/ Pre-Print: bioRxiv
Key Words: mAbs, B cell, neutralisation, SARS-Cov2 RBD, cross-reactivity, ACE2
1. Isolation of 206 RBD SARS-COV2 specific mABs from 8 COVID-19 positive patients and characterization of their binding affinity and neutralization capacity.
2. mAbs sequence comparison show no discernable pattern of VH usage and the presence of different clones with more or less divergence from germline clones.
3. No cross-reactivity of RBD SARS-COV 2 specific antibodies with RBDs from SARS-COV and MERS-COV.
4. Identification of two good mAbs candidates P2B-2F6 and P2C-1F11 for prophylactic and therapeutic intervention.
This study aims to characterize and compare antibodies generated during the course of SARS-COV2 infection. Using IgG+ve B cells isolated from 8 covid-19 patients, the authors generate a library of 206 recombinant mAbs specific for SARS-COV2 Receptor Binding Domains (RBD). Comparison of genetic sequences between the various antibodies demonstrated no discernable pattern of VH usage. Characterization of the binding affinity by surface plasmon resonance and neutralization capacity againsts SARS-COV2 pseudovirus were measured and revealed some potential mAb candidates for recombinant mAb therapy that recognize both overlapping and distinct epitopes of the RBD of SARS-COV2. Surprisingly, there was no cross-reactivity of the antibodies isolated with RBDs from SARS-COV or MERS-COV highlighting the diverse antigenicity of the different virus RBD and suggesting that recombinant mAb therapy and vaccines may have to specifically target the RBD of each viral species independently to achieve efficacy.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19: The study demonstrates there to be high variability within the immunogenic response of COVID-19 patients, and requires further follow-up with a greater number of patient samples to identify potential commonalities within the B cell and antibody response.
Understand the virology and/or cell biology of SARS-CoV2/COVID19: This study identifies that RBD cross-reactivity does not necessarily correlate with Spike protein cross-reactivity, and in fact identifies that there is little RBD cross-reactivity of SARS-CoV2 with SARS-CoV and Mers-CoV.
Develop a vaccine for SARS-CoV2/COVID19: The study demonstrates that patient-derived antibodies recognize overlapping and distinct epitopes of SARS-CoV2 RBD, which suggests that vaccination strategies could potentially elicit a synergistic antiviral effect by targeting multiple epitopes.
Treatment of SARS-CoV2/COVID19 positive individuals: The fact that there is little RBD cross-reactivity with SARS-CoV and MERS-CoV suggests that transfusions of plasma from
patients infected with SARS-CoV or MERS-CoV may not be an effective strategy for treatment of SARS-CoV-2 patients, although neutralizing antibodies targeting other more conserved regions of S may be useful.
· bioinformatics study (analysis of the antibody sequences)
· In vitro study
· Clinical Cohort study (8 patients)
Strengths and limitations of the paper
Novelty: The authors identify mAbs with good affinity and neutralisation capacity. In addition, they reveal that against expectations, SARS-COV2 RBD specific antibodies don’t recognise the RBD of SARS-COV or MERS-COV, pointing out that vaccine strategies may have to target each viral species differently.
Standing in the field: Previous studies have reported potential neutralising antibodies against Spike protein that could be useful therapeutics.
Appropriate statistics: There are no statistics provided in this study but most of the time the 8 patients profile is shown.
Viral model used: Primarily SARS-CoV2 pseudovirus; minimal use of SARS-CoV2 (live).
Translatability: There is a direct translational potential. This study identifies potential mAb candidates for the development of recombinant antibody treatment of COVID-19 patients. In addition, it highlights the variable antigenicity of the different virus RBDs pointing out the need for virus-specific vaccine design strategies if based upon the RBD.
- Neutralisation is mainly assessed using pseudovirus. They use SARS-COV2 for an in vitro cytopathic effect assay that is not quantitative. Additionally, the data provided are not convincing of neutralisation effects of live virus (Figure 4).
- Limited number of samples that don’t allow them to draw significant conclusions concerning relationships between the humoral response raised and the disease severity.
- Study did not include an in vivo model – it would be necessary to validate the efficacy of the identified neutralising monoclonal antibodies in vivo prior to translation to therapeutic use.