Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo
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Abstract
SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.
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SciScore for 10.1101/2020.09.15.298067: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Mouse studies and in vivo infections: All mouse studies were performed at the University of North Carolina (Animal Welfare Assurance #A3410-01) using protocols (19-168, 20-114) approved by the UNC Institutional Animal Care and Use Committee (IACUC). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Twelve month old female BALB/c mice (Envigo, #047) were inoculated with the indicated concentration of antibody intraperitoneally 12 hours prior to infection. Cell Line Authentication Contamination: All cell lines have been tested negative for contamination with mycoplasma and parental cell lines were obtained … SciScore for 10.1101/2020.09.15.298067: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Mouse studies and in vivo infections: All mouse studies were performed at the University of North Carolina (Animal Welfare Assurance #A3410-01) using protocols (19-168, 20-114) approved by the UNC Institutional Animal Care and Use Committee (IACUC). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Twelve month old female BALB/c mice (Envigo, #047) were inoculated with the indicated concentration of antibody intraperitoneally 12 hours prior to infection. Cell Line Authentication Contamination: All cell lines have been tested negative for contamination with mycoplasma and parental cell lines were obtained from the ATCC. Table 2: Resources
Antibodies Sentences Resources The half-maximal and 90% inhibitory concentrations (IC50 and IC90) for monoclonal antibodies were determined using 4-parameter nonlinear regression (GraphPad Prism). IC90suggested: NoneExperimental Models: Cell Lines Sentences Resources For constitutive expression of murine Ace2 (muAce2) in HT1080 cells, a cDNA encoding muAce2 was inserted into a lentiviral vector CSIB 3’ to the SFFV promoter. HT1080suggested: CLS Cat# 300216/p517_HT-1080, RRID:CVCL_0317)HT1080muAce2 cells were generated by transduction with CSIB-based virus followed by selection with 5 μg/ml blasticidin. HT1080muAce2suggested: NoneFor virus titration, the caudal lobe of the right lung was homogenized in PBS, resulting homogenate was serial-diluted and inoculated onto confluent monolayers of Vero E6 cells, followed by agarose overlay. Vero E6suggested: RRID:CVCL_XD71)SARS-CoV-2/SARS-CoV-2 MA pseudotyped reporter virus: SARS-CoV-2 pseudotyped particles were produced by co-transfection of pNL4-3ΔEnv-nanoluc and pSARS-CoV-2-MA-Strunc in 293T cell (Schmidt et al., 2020, Robbiani et al., 2020). 293Tsuggested: NoneExperimental Models: Organisms/Strains Sentences Resources Twelve month old female BALB/c mice (Envigo, #047) were inoculated with the indicated concentration of antibody intraperitoneally 12 hours prior to infection. BALB/csuggested: NoneSoftware and Algorithms Sentences Resources The half-maximal and 90% inhibitory concentrations (IC50 and IC90) for monoclonal antibodies were determined using 4-parameter nonlinear regression (GraphPad Prism). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results 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: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
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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