SARS-CoV-2 Delta Variant Displays Moderate Resistance to Neutralizing Antibodies and Spike Protein Properties of Higher Soluble ACE2 Sensitivity, Enhanced Cleavage and Fusogenic Activity

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1. Version published to 10.3390/v13122485

   Dec 11, 2021
2. 

   ScreenIT

   Nov 19, 2021

   SciScore for 10.1101/2021.11.05.467523: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	Consent: Vaccine-elicited sera were collected at the U.S. Food and Drug Administration with written consent under an approved Institutional Review Board (IRB) protocol (FDA IRB Study # 2021-CBER-045). IRB: Vaccine-elicited sera were collected at the U.S. Food and Drug Administration with written consent under an approved Institutional Review Board (IRB) protocol (FDA IRB Study # 2021-CBER-045).
   Sex as a biological variable	Donors were 18-73 years old with six males/four females.
   Randomization	not detected.
   Blinding	Due to a confidentiality agreement with the manufacturers, neutralizing antibodies described are shown with blinded identification codes as follows: single neutralizing antibodies (nAbs …

   SciScore for 10.1101/2021.11.05.467523: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	Consent: Vaccine-elicited sera were collected at the U.S. Food and Drug Administration with written consent under an approved Institutional Review Board (IRB) protocol (FDA IRB Study # 2021-CBER-045). IRB: Vaccine-elicited sera were collected at the U.S. Food and Drug Administration with written consent under an approved Institutional Review Board (IRB) protocol (FDA IRB Study # 2021-CBER-045).
   Sex as a biological variable	Donors were 18-73 years old with six males/four females.
   Randomization	not detected.
   Blinding	Due to a confidentiality agreement with the manufacturers, neutralizing antibodies described are shown with blinded identification codes as follows: single neutralizing antibodies (nAbs A to R), combination of two neutralizing antibodies (cnAbs S to X), and polyclonal neutralizing antibodies (pnAbs III to IV).
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   Twenty-three therapeutic neutralizing antibodies against SARS-COV-2 spike protein were generously donated by different pharmaceutical companies for the U.S.	SARS-COV-2 spike protein suggested: None
   Experimental Models: Cell Lines
   Sentences	Resources
   2.4. soluble ACE2 production: The production of His-tagged soluble ACE2 was performed in FreeStyle™ 293-F cells and purified using HisPur™ Ni-NTA Resin (Thermo Scientific) as described previously [31]. 2.5.	293-F suggested: RRID:CVCL_6642)
   For ACE2 neutralization assay, serially diluted recombinant human soluble ACE2 was incubated with indicated pseudovirus (~1×106 RLU / ml) for one hour at 37°C and 100 μl of pseudovirus and soluble ACE2 mixture was added to 293T-ACE2.TMPRSS2 cells.	293T-ACE2.TMPRSS2 suggested: None
   Spike-transfected/β-Gal ω subunit-expressing 293T cells were mixed with β-Gal α subunit-transfected/293T-ACE2.TMPRSS2 cells at 1:1 ratio to a total of 6 x 104 cells per well on a 96-well plate.	293T suggested: None
   Recombinant DNA
   Sentences	Resources
   Plasmids and cell lines: Codon-optimized full-length open reading frames of the S genes of SARS-COV-2 variants were cloned into pcDNA3.1(+) or pVRC8400 by GenScript (Piscataway, NJ).	pVRC8400 suggested: RRID:Addgene_63164)
   The HIV gag/pol (pCMVΔR8.2), and Luciferase reporter (pHR’CMV-Luc) plasmids were obtained from the Vaccine Research Center (National Institutes of Health, Bethesda, MD) [28,29].	pHR’CMV-Luc suggested: None
   Briefly, pseudoviruses bearing the spike glycoprotein and packaging a firefly luciferase (FLuc) reporter gene were produced in 293T cells by co-transfection of 5μg of pCMVΔR8.2, 5μg of pHR’CMVLuc and 4μg of pcDNA3.1(+) or 0.5 ug of pVRC8400-encoding a codon-optimized spike gene with the desired substitutions.	pCMVΔR8.2 suggested: None pcDNA3.1 suggested: RRID:Addgene_79663)
   Software and Algorithms
   Sentences	Resources
   Furin prediction score calculations: The prediction of furin-specific cleavage site in spike proteins were computed using the ProP 1.0 Server hosted at http://www.cbs.dtu.dk/services/ProP/ and the PiTou V3 software hosted at http://www.nuo-lan.net/reference.html. 2.10.	http://www.cbs.dtu.dk/services/ProP/ suggested: (ProP Server, RRID:SCR_014936)
   Statistics analysis: One-way analysis of variance (ANOVA) with Dunnett’s multiple comparisons tests (variants compared to WT(D614G)), Mann-Whitney test for the comparison of two groups with unmatched pairs (Pfizer BNT162b2 compared to Moderna) and geometric mean titers (GMT) with 95% confidence intervals were performed using GraphPad Prism software.	GraphPad Prism suggested: (GraphPad Prism, RRID:SCR_002798)

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   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).

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   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.

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   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).

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   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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   Results from scite Reference Check: We found no unreliable references.

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3. 

   Version published to 10.1101/2021.11.05.467523v1 on bioRxiv

   Nov 8, 2021