Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2

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1. Version published to 10.1038/s41564-022-01163-3

   Jul 14, 2022
2. 

   ScreenIT

   Dec 30, 2021

   SciScore for 10.1101/2021.12.23.21268293: (What is this?)

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

   Table 1: Rigor

   Ethics	not detected.
   Sex as a biological variable	not detected.
   Randomization	Multidimensional scaling was carried out with 1000 random restart optimisations, to avoid local optima and increase the likelihood of finding the best fit to the measured titres.
   Blinding	not detected.
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   The binding of IgG on the plate surface was detected by using an anti-human IgG horseradish peroxidase antibody conjugate (Sigma-Aldrich, Poole, UK) and 3,3′,5,5′-Tetramethylbenzidine (Europa Bioproducts Ltd, Ely, UK).	anti-human IgG suggested: None
   Nucleoprotein (N) antibodies were measured as a marker of previous …

   SciScore for 10.1101/2021.12.23.21268293: (What is this?)

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

   Table 1: Rigor

   Ethics	not detected.
   Sex as a biological variable	not detected.
   Randomization	Multidimensional scaling was carried out with 1000 random restart optimisations, to avoid local optima and increase the likelihood of finding the best fit to the measured titres.
   Blinding	not detected.
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   The binding of IgG on the plate surface was detected by using an anti-human IgG horseradish peroxidase antibody conjugate (Sigma-Aldrich, Poole, UK) and 3,3′,5,5′-Tetramethylbenzidine (Europa Bioproducts Ltd, Ely, UK).	anti-human IgG suggested: None
   Nucleoprotein (N) antibodies were measured as a marker of previous SARS-CoV-2 infection (Anti-SARS-CoV-2 total antibody assay, Roche Diagnostics, Basel, Switzerland) and spike (S) protein antibodies were measured as an indication of infection or vaccination (Elecsys Anti-SARS-CoV-2 S total antibody assay, Roche Diagnostics: positive ≥ 0.8 arbitrary units (au)/mL to assess vaccine response).	Anti-SARS-CoV-2 suggested: None
   Experimental Models: Cell Lines
   Sentences	Resources
   Cells: Human embryonic kidney (HEK) 293T cells were used to generate lentiviral pseudoparticles bearing the SARS-CoV-2 spike.	HEK suggested: None 293T suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
   HEK293T cells stably expressing human angiotensin converting enzyme 2 (hACE2) under 1µg/mL puromycin (Gibco) selection were used for neutralisation assays [56].	HEK293T suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
   Recombinant DNA
   Sentences	Resources
   Briefly, cells were transfected with 900 ng of SARS-CoV-2 spike (see Supplemental Table 1), 600 ng p8.91 (encoding for HIV-1 gag-pol), 600 ng CSFLW	p8.91 suggested: None

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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: We detected the following sentences addressing limitations in the study:

   One limitation of our study is that for some VOCs, e.g. Beta, almost all the sera dropped below the limit of detection of our assay (ND80 of 10), providing less granularity, complicating comparisons with other studies, and obfuscating correlations with more sensitive Ab-detection assays such as the RBD-ELISA. Elsewhere, our data on Omicron neutralisation following 2 doses of BNT162b2 fits with recently reported findings. Dejnirattisai et al., Cameroni et al., and Garcia-Beltran et al. all showed drops in neutralisation of >30-fold [18-20, 30]. However, it is clear from our data, and that of Garcia-Beltran et al., [20] that boosting with a 3rd dose of BNT162b2 generates a much higher overall titre of neutralising antibodies to D614G (median ND80 ≥3070.9 in the 70-79 age group, Figure 4B) and that these high titres enhance cross-protection against Omicron and mitigate against the significant drops in neutralisation seen after two doses, highlighting the important role of boosters in providing robust long-term immunity to SARS-CoV-2. A smaller pool of antigenicity data is available on the wide range of other variants (VUIs/VUMs) that have emerged since the beginning of the pandemic. Our data highlighted several important antigenically-divergent variants, in particular C.1.2 and B.1.638 (Note: B.1.638 is from a small isolated outbreak; n=13), both initially detected in South Africa [31]; B.1.621 (Mu), first detected in Colombia [32] and P.3 (Theta) – isolated in the Philippines [...

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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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 10.1101/2021.12.23.21268293v1 on medRxiv

   Dec 24, 2021