AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein–specific T H 1 response with a diverse TCR repertoire

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Abstract

Polyfunctional CD4 + and CD8 + T cell responses are elicited against the SARS-CoV-2 spike protein after two doses of the AZD1222 COVID-19 vaccine.

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  1. SciScore for 10.1101/2021.06.17.21259027: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Written informed consent was obtained from all participants, and the trials were done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.
    IRB: COV001 was approved in the UK by the Medicines and Healthcare products Regulatory Agency (reference 21584/0424/001-0001) and the South-Central Berkshire Research Ethics Committee (reference 20/SC/0145).
    Sex as a biological variablenot detected.
    RandomizationStudy design: Healthy adults aged 18 to ≥70 years were enrolled in a single-blind, randomized, controlled, phase 2/3 trial for the SARS-CoV-2 vaccine, AZD1222 (ChAdOx1 nCoV-19) as described in the previously published safety and immunogenicity report (13).
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: Extracted genomic DNA was amplified in a bias-controlled multiplex polymerase chain reaction (PCR), followed by high-throughput sequencing.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Samples were analyzed using FlowJo 10.6.2.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Assay qualification was performed by the Vaccine Immunology Program at the Vaccine Research Center, National Institute of Allergy and Infectious Diseases,
    Vaccine Immunology Program
    suggested: None

    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: We detected the following sentences addressing limitations in the study:
    Limitations of the study included that it was run in the UK, with a majority of participants who were white and of British descent, and with more females than males in the overall population. This may have therefore resulted in underestimating clonal diversity induced by AZD1222, due to a population with a more limited HLA profile and may be a factor responsible for reduced spike-specific CD8+ T-cell clonal diversity and lower frequencies compared with corresponding Th1 responses. Furthermore, spike-specific CD8+ T-cell frequencies may have been reduced because samples were analyzed at Day 28 post vaccination, which is 2 weeks past the peak timepoint of the T-cell responses (13). Lack of availability of biospecimens at this timepoint in the present study prevented analyses of AZD1222-induced T-cell responses against SARS-CoV-2 and characterization of the TCR repertoire at this peak timepoint. Furthermore, in this study, only six participants vaccinated with AZD1222 were seropositive at Day 0, providing limited data for the effect of AZD1222 vaccination on seropositive participants. Despite these study limitations, our observations are still consistent with data that SARS-CoV-2–specific CD4+ T-cell responses are more prominent than CD8+ T-cell responses following infection (31) and vaccination (7, 8, 10). In summary, a combination of antibody and T-cell immunity is likely needed to provide long-term protection against SARS-CoV-2 infection (40). Previous studies have shown that...

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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


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