Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines

  1. Maria Prendecki
  2. Tina Thomson
  3. Candice L. Clarke
  4. Paul Martin
  5. Sarah Gleeson
  6. Rute Cardoso De Aguiar
  7. Helena Edwards
  8. Paige Mortimer
  9. Stacey McIntyre
  10. Shanice Lewis
  11. Jaid Deborah
  12. Alison Cox
  13. Graham Pickard
  14. Liz Lightstone
  15. David Thomas
  16. Stephen P. McAdoo
  17. Peter Kelleher
  18. Michelle Willicombe
  19. in collaboration with the OCTAVE Study Consortium

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Abstract

Background

Attenuated immune responses to mRNA SARS-CoV-2 vaccines have been reported in solid organ transplant recipients. Most studies have assessed serological responses alone, and there is limited immunological data on vector-based vaccines in this population. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in a cohort of kidney transplant patients, assessing both serological and cellular responses.

Methods

920 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=490) or ChAdOx1 (n=430). 106 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group.

Results

Anti-S was detected in 569 (61.8%) patients. Seroconversion rates in infection-naïve patients who received BNT162b2 were higher compared with ChAdOx1, at 269/410 (65.6%) and 156/358 (43.6%) respectively, p<0.0001. Anti-S concentrations were higher following BNT162b, 58(7.1-722) BAU/ml, compared with ChAdOx1, 7.1(7.1-39) BAU/ml, p<0.0001. Calcineurin inhibitor monotherapy, vaccination occurring >1 st year post-transplant and receiving BNT162b2 was associated with seroconversion.

Only 28/106 (26.4%) of patients had detectable T-cell responses. There was no difference in detection between infection-naïve patients who received BNT162b2, 7/40 (17.5%), versus ChAdOx1, 2/39 (5.1%), p=0.15. There was also no difference in patients with prior infection who received BNT162b2, 8/11 (72.7%), compared with ChAdOx1, 11/16 (68.8%), p=0.83.

Conclusions

Enhanced humoral responses were seen with BNT162b2 compared with ChAdOx1 in kidney transplant patients. T-cell responses to both vaccines were markedly attenuated. Clinical efficacy data is still required but immunogenicity data suggests weakened responses to both vaccines in transplant patients, with ChAdOx1 less immunogenic compared with BNT162b2.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.09.21260192: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The OCTAVE study was approved by the Health Research Authority, Research Ethics Committee (Reference:21/HRA/0489).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological testing: Serum was tested for antibodies to both the nucleocapsid protein (anti-NP) and spike protein (anti-S).
    anti-NP
    suggested: None
    For vaccine responses, spike protein antibodies (anti-S IgG) were assessed using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA.
    anti-S IgG
    suggested: None
    Anti-S antibody titres are quantitative with a threshold value of 7.1 BAU/ml for positivity, and an upper level of detection of 5680 BAU/ml.
    Anti-S
    suggested: None
    As part of this protocol, patients were initially screened for anti-NP, and those with a subthreshold anti-NP index value (0.25-1.4), underwent confirmatory testing for natural infection by assessing for receptor binding domain (anti-RBD) antibodies.
    anti-RBD
    suggested: None
    This was performed using an in-house double binding antigen ELISA (Imperial Hybrid DABA; Imperial College London, London, UK), which detects total RBD antibodies(14-17).
    in-house double binding antigen ELISA
    suggested: None
    antibodies(14-17
    suggested: None
    Software and Algorithms
    SentencesResources
    The first is the OCTAVE study, an Observational Cohort Study of T-cells, Antibodies and Vaccine Efficacy in SARS-CoV-2 in people with chronic diseases and/or secondary immunodeficiency, which is part of the UK COVID-19 Immunity National Core Study Programme.
    OCTAVE
    suggested: (GNU Octave, RRID:SCR_014398)
    For vaccine responses, spike protein antibodies (anti-S IgG) were assessed using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA.
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Statistical Analysis: Statistical analysis was conducted using Prism 9.0 (GraphPad Software Inc., San Diego, California).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    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:
    This study has several limitations, some of which have already been outlined above. In addition, it is important we highlight that the subgroup of patients who underwent T-cell analysis differ from the main cohort. They were younger, more likely to have been vaccinated in the first-year post-transplant and received their 2nd dose of vaccine at a shorter interval compared with the main cohort, albeit at a median time of >8 weeks. This reflected clinical prioritisation for newly transplanted patients, with a high exposure risk, to be vaccinated first. Also, the healthy control reference group, is not a matched control group, with healthcare workers being significantly younger than our patient cohort, which independently could result in better immunological responses independent of immunosuppression. Notwithstanding these limitations, this study has demonstrated markedly diminished humoral and cellular immune responses to both the BNT162b2 and ChAdOx1 vaccines in kidney transplant patients. No enhanced cellular responses were seen with ChAdOx1, however our results do demonstrate inferior serological responses in patient’s receiving ChAdOx1 compared with BNT162b2. Although it is acknowledged that immunogenicity of vaccines does not necessarily equate to clinical efficacy in this immunosuppressed or other populations, emerging data of SARS-CoV-2 related deaths in transplant recipients, may suggest a correlation between absence of detectable immunological response and efficacy(26, ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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).

    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.

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

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.07.09.21260192v1 on medRxiv