Human immunoglobulin from transchromosomic bovines hyperimmunized with SARS-CoV-2 spike antigen efficiently neutralizes viral variants
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with amino-acid substitutions and deletions in spike protein (S) can reduce the effectiveness of monoclonal antibodies (mAbs) and may compromise immunity induced by vaccines. We report a polyclonal, fully human, anti-SARS-CoV-2 immunoglobulin produced in transchromosomic bovines (Tc-hIgG-SARS-CoV-2) hyperimmunized with two doses of plasmid DNA encoding the SARS-CoV-2 Wuhan strain S gene, followed by repeated immunization with S protein purified from insect cells. The resulting Tc-hIgG-SARS-CoV-2, termed SAB-185, efficiently neutralizes SARS-CoV-2, and vesicular stomatitis virus (VSV) SARS-CoV-2 chimeras in vitro . Neutralization potency was retained for S variants including S477N, E484K, and N501Y, substitutions present in recent variants of concern. In contrast to the ease of selection of escape variants with mAbs and convalescent human plasma, we were unable to isolate VSV-SARS-CoV-2 mutants resistant to Tc-hIgG-SARS-CoV-2 neutralization. This fully human immunoglobulin that potently inhibits SARS-CoV-2 infection may provide an effective therapeutic to combat COVID-19.
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SciScore for 10.1101/2021.02.06.430072: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The animal protocols contained in the study were approved by SAB Biotherapeutic Institutional Animal Care and Use Committee (IACUC). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Determination of SARS CoV-2 spike protein-specific human IgG antibody titers was performed in Maxisorp Immuno 96-well ELISA plates (Thermo Scientific) coated overnight at 4°C with 100 μl/well of 2 μg ml−1 recombinant SARS CoV-2 spike protein produced and purified from 293 cells in PBS. human IgGsuggested: NoneAfter final washing … SciScore for 10.1101/2021.02.06.430072: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The animal protocols contained in the study were approved by SAB Biotherapeutic Institutional Animal Care and Use Committee (IACUC). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Determination of SARS CoV-2 spike protein-specific human IgG antibody titers was performed in Maxisorp Immuno 96-well ELISA plates (Thermo Scientific) coated overnight at 4°C with 100 μl/well of 2 μg ml−1 recombinant SARS CoV-2 spike protein produced and purified from 293 cells in PBS. human IgGsuggested: NoneAfter final washing with PBST, the bound anti-spike antibodies were detected colorimetrically by using the 3, 3,’ 5, 5’-tetramethylbenzidine (TMB) substrate kit (SeraCare). anti-spikesuggested: NoneExperimental Models: Cell Lines Sentences Resources VSV-SARS-CoV-2 plaque assays were performed on Vero and Vero E6-TMPRSS2 cells. Vero E6-TMPRSS2suggested: NoneSAB-185 pAb-virus complexes then were added to Vero E6 cells in 96-well plates and incubated at 37 °C for 7.5 h. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources The Tc bovines used in this study are homozygous for either triple or quadruple knock-outs in the endogenous bovine immunoglobulin genes (IGHM − / − IGHML1 − / − IGL − / − or IGHM − / − IGHML1 − / − IGL − / − /IGK− / −) and carry a human artificial chromosome (HAC) vector labeled as isKcHACD with an IgG1 production bias. IGHM − / − IGHML1 − / − IGL − / − or IGHM − / − IGHML1 − / − IGL − / − /IGK− / −suggested: NoneSoftware and Algorithms Sentences Resources Plasma was collected using an automated plasmapheresis system (Baxter Healthcare, Autopheresis C Model 200). Baxter Healthcaresuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT02788188 Completed Safety, Tolerability, and Pharmacokinetics of SAB-301 in Hea… NCT02508584 Completed Personalized Immunotherapeutic for Antibiotic-resistant Infe… NCT04468958 Recruiting Safety, Tolerability, and Pharmacokinetics of SAB-185 in Hea… NCT0446917 Trial number did not resolve on clinicaltrials.gov. Is the number correct? NA Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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