Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity

Article activity feed

1. Version published to 10.1038/s41586-021-04085-y

   Oct 11, 2021
2. 

   ScreenIT

   Jul 20, 2021

   SciScore for 10.1101/2021.07.14.21260307: (What is this?)

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

   Table 1: Rigor

   Ethics	IRB: Ethics statement: This study was approved by Yale Human Research Protection Program Institutional Review Board (IRB Protocol ID 2000028924). Consent: Informed consent was obtained from all enrolled vaccinated HCWs.
   Sex as a biological variable	not detected.
   Randomization	not detected.
   Blinding	ELISA, neutralizations, and flow cytometry analyses were blinded.
   Power Analysis	not detected.
   Cell Line Authentication	Contamination: The cell line was obtained from the ATCC and has been tested negative for contamination with mycoplasma.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   Human Anti-Spike and anti-nucleocapsid antibodies were serially diluted to generate a standard curve.	anti-nucleocapsid suggest…

   SciScore for 10.1101/2021.07.14.21260307: (What is this?)

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

   Table 1: Rigor

   Ethics	IRB: Ethics statement: This study was approved by Yale Human Research Protection Program Institutional Review Board (IRB Protocol ID 2000028924). Consent: Informed consent was obtained from all enrolled vaccinated HCWs.
   Sex as a biological variable	not detected.
   Randomization	not detected.
   Blinding	ELISA, neutralizations, and flow cytometry analyses were blinded.
   Power Analysis	not detected.
   Cell Line Authentication	Contamination: The cell line was obtained from the ATCC and has been tested negative for contamination with mycoplasma.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   Human Anti-Spike and anti-nucleocapsid antibodies were serially diluted to generate a standard curve.	anti-nucleocapsid suggested: None
   Plates were washed three times with PBS-T (PBS with 0.1% Tween-20) and 50 μl of HRP anti-Human IgG Antibody (GenScript #A00166, 1:5,000) diluted in dilution solution added to each well.	anti-Human IgG suggested: None
   Flow cytometry: Antibody clones and vendors were as follows: BB515 anti-hHLA-DR (G46-6) (1:400	anti-hHLA-DR ( G46-6 ) suggested: None
   Experimental Models: Cell Lines
   Sentences	Resources
   Briefly, 300 µl of serial fold virus dilutions were used to infect Vero E6 cells in MEM supplemented NaHCO3, 4% FBS 0.6% Avicel RC-581.	Vero E6 suggested: None
   Software and Algorithms
   Sentences	Resources
   Ethics statement: This study was approved by Yale Human Research Protection Program Institutional Review Board (IRB Protocol ID 2000028924).	Yale Human Research Protection Program suggested: None
   The Institutional Review Board from the Yale University Human Research Protection Program determined that the RT-qPCR testing and sequencing of de-identified remnant COVID-19 clinical samples conducted in this study is not research involving human subjects (IRB Protocol ID: 2000028599).	Human Research Protection Program suggested: None
   The clinical data were collected using EPIC EHR May 2020 and REDCap 9.3.6 software.	REDCap suggested: (REDCap, RRID:SCR_003445)
   Data were analysed using FlowJo software version 10.6 software (Tree Star).	FlowJo suggested: (FlowJo, RRID:SCR_008520)
   Statistical analysis: All analyses of patient samples were conducted using GraphPad Prism 8.4.3, JMP 15, and R 3.4.3.	GraphPad Prism suggested: (GraphPad Prism, RRID:SCR_002798)

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   Results from OddPub: Thank you for sharing your code and data.

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   A potential limitation in our study is that, even with our 7-day stimulation prior to analysis, it remains possible that our T cells assay failed to detect underrepresented T cell clones impacted by variant sequences when sampled in the presence of the majority of conserved peptides. Overall, our data point to a necessity of active monitoring of T cell reactivity in the context of SARS-CoV-2 evolution. The magnitude of the antibody titers in COVID-19 patients following natural infection has been directly correlated with length of infection and severity31. Here, we found that previously infected vaccinated individuals display an increased resilience in antibody responses against both “single” and combination of substitutions in the RBD region, which otherwise severely decreased neutralization activity of uninfected vaccinated individuals. Our observations of the impact of pre-existing immunity in vaccinated individuals on their ability to neutralize variants could be explained by the time window between the initial exposure (infection) and vaccination. Still, our observations provide an important rationale for worldwide efforts in characterizing the contribution of pre-existing SARS-CoV-2 immunity to the outcome of various vaccination strategies. Along with recently introduced serological tests32, such studies could inform evidence-based risk evaluation, patient monitoring, adaptation of containment methods and vaccine development and deployment. Finally, these findings sugges...

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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 10.1101/2021.07.14.21260307v1 on medRxiv

   Jul 18, 2021