A combination of two human neutralizing antibodies prevents SARS-CoV-2 infection in rhesus macaques
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Abstract
Human monoclonal antibody (mAb) treatments are promising for COVID-19 prevention, post-exposure prophylaxis, or therapy. However, the titer of neutralizing antibodies required for protection against SARS-CoV-2 infection remains poorly characterized. We previously described two potently neutralizing mAbs COV2-2130 and COV2-2381 targeting non-overlapping epitopes on the receptor-binding domain of SARS-CoV-2 spike protein. Here, we engineered the Fc-region of these mAbs with mutations to extend their persistence in humans and reduce interactions with Fc gamma receptors. Passive transfer of individual or combinations of the two antibodies (designated ADM03820) given prophylactically by intravenous or intramuscular route conferred virological protection in a non-human primate (NHP) model of SARS-CoV-2 infection, and ADM03820 potently neutralized SARS-CoV-2 variants of concern in vitro . We defined 6,000 as a protective serum neutralizing antibody titer in NHPs against infection for passively transferred human mAbs that acted by direct viral neutralization, which corresponded to a concentration of 20 μg/mL of circulating mAb.
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SciScore for 10.1101/2021.09.27.462074: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Studies were conducted in compliance with all relevant local, state, and federal regulations and were approved by the Bioqual Institutional Animal Care and Use Committee (IACUC).
IACUC: Studies were conducted in compliance with all relevant local, state, and federal regulations and were approved by the Bioqual Institutional Animal Care and Use Committee (IACUC).Sex as a biological variable Cynomolgus monkeys (Macaca fascicularis) (2.2 – 5.8 kg body weight; 6 to 12 years old) were mixed male and female and randomly assigned to groups. Randomization Cynomolgus monkeys (Macaca fascicularis) (2.2 – 5.8 kg body weight; 6 to 12 years old) were mixed male and female and randomly … SciScore for 10.1101/2021.09.27.462074: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Studies were conducted in compliance with all relevant local, state, and federal regulations and were approved by the Bioqual Institutional Animal Care and Use Committee (IACUC).
IACUC: Studies were conducted in compliance with all relevant local, state, and federal regulations and were approved by the Bioqual Institutional Animal Care and Use Committee (IACUC).Sex as a biological variable Cynomolgus monkeys (Macaca fascicularis) (2.2 – 5.8 kg body weight; 6 to 12 years old) were mixed male and female and randomly assigned to groups. Randomization Cynomolgus monkeys (Macaca fascicularis) (2.2 – 5.8 kg body weight; 6 to 12 years old) were mixed male and female and randomly assigned to groups. Blinding These studies were not blinded. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were washed and sequentially incubated with an oligoclonal pool of SARS2-2, SARS2-11, SARS2-16, SARS2-31, SARS2-38, SARS2-57 and SARS2-71 anti-S (VanBlargan et al., 2021) antibodies and HRP-conjugated goat anti-mouse IgG (Sigma, 12-349) in PBS supplemented with 0.1% saponin and 0.1% bovine serum albumin. SARS2-38suggested: NoneSARS2-57suggested: Noneanti-Ssuggested: Noneanti-mouse IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, stably transfected CHO cells expressing either COV2-2130-YTE-LALA or COV2-2381-YTE-LALA were generated using Leap-In transposon vectors (ATUM) containing the respective antibody heavy and light chain genes and a glutamine synthetase gene as a selectable marker. CHOsuggested: NoneThe viral stocks were expanded using Vero E6 cells and harvested on day 5 following inoculation. Vero E6suggested: RRID:CVCL_XD71)Antibody–virus complexes were added to Vero-TMPRSS2 cell monolayers in 96-well plates and incubated at 37 °C for 1 h. Vero-TMPRSS2suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)Software and Algorithms Sentences Resources The time-weighted average (TWA) values for the change of sgRNA viral load in BAL or NP from day 1 to day 10 after viral challenge were calculated as the area under the curve (AUC) of the change in viral load in Prism (version 9.1.2; GraphPad) and then divided by 10 as described previously (Baum et al., 2020a) (Table S1). Prismsuggested: (PRISM, RRID:SCR_005375)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)The fitting curves and confidence intervals to visualize the relationship between TWA and antibody levels were estimated using Lowess curve smoothing method using ggplot2 in R software. ggplot2suggested: (ggplot2, RRID:SCR_014601)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.
Results from scite Reference Check: We found no unreliable references.
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