Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

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Abstract

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age 1 . Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine 2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.

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  1. SciScore for 10.1101/2021.02.03.21251054: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the East of England – Cambridge Central Research Ethics Committee (17/EE/0025).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    PBMCs were stained with 2ul of each antibody: anti-CD3-fluorescein isothiocyanate (FITC), clone UCHT1; anti-CD4-phycoerythrin (PE), clone RPA-T4; anti-CD8a-peridinin-chlorophyll
    anti-CD3-fluorescein
    suggested: None
    anti-CD4-phycoerythrin
    suggested: None
    anti-CD8a-peridinin-chlorophyll
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus neutralisation assays were performed on 293T cell transiently transfected with ACE2 and TMPRSS2 using SARS-CoV2 Spike pseudotyped virus expressing luciferase23.
    293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analysed with FlowJo v10 (Becton Dickinson, Wokingham, UK).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Developed plates were read using an AID iSpot reader (Oxford Biosystems, Oxford, UK) and counted using AID EliSpot v7 software (Autoimmun Diagnostika GmbH, Strasberg, Germany).
    Oxford Biosystems
    suggested: (Science Exchange, RRID:SCR_010620)
    IC50 values were calculated in GraphPad Prism.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Here we have addressed an important aspect of rollout of vaccination against SARS-CoV-2, where the second dose may be delayed due to supply limitations. We have shown that almost half of individuals above the age of 80 have a suboptimal neutralising antibody response three weeks after vaccination with BNT162b2, and that the second dose is associated with robust neutralising responses. T cell responses were generally good across age groups following first dose, though lower in the over 80 age group. Binding IgA antibodies to Spike and RBD increased following the first and second doses, mirroring levels seen in natural infection. IgG3 responses to Spike and RBD increased predominantly after the second dose; this subclass has been associated with multifunctional antibody responses. In a clinical study specifically looking at older adults vaccinated with BNT162b2 the GMT (geometric mean titre) after first dose was 12 in a set of 12 subjects between ages of 65 and 85 years, rising to 149 seven days after the second dose 3. Whilst the GMT after second dose was lower in older subjects, the data for first dose were unclear, possibly due to neutralisation assay characteristics. Furthermore, in the Moderna 1273 mRNA vaccine study in older individuals (above 55 years), neutralisation was only detectable after the second dose, whilst binding antibodies were detectable after both doses9. Interestingly, in aged mice the ChAdOx nCov-19 vaccine responses were lower as compared to younger mic...

    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.

    About SciScore

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