Comparative immunogenicity of heterologous versus homologous 3rd SARS-CoV-2 vaccine doses in kidney transplant recipients

  1. Tina Thomson
  2. Maria Prendecki
  3. Sarah Gleeson
  4. Paul Martin
  5. Katrina Spensley
  6. Charlotte Seneschall
  7. Jaslyn Gan
  8. Candice L. Clarke
  9. Shanice Lewis
  10. Graham Pickard
  11. David Thomas
  12. Stephen P. McAdoo
  13. Liz Lightstone
  14. Alison Cox
  15. Peter Kelleher
  16. Michelle Willicombe

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Abstract

Background

Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. Emerging evidence suggests at least equivalent immunogenicity of heterologous compared with homologous vaccine regimens in the general population. In this study, we report on immune responses to 3 rd dose BNT162b2 vaccines in transplant recipients either primed with ChAdOx1 or BNT162b2.

Methods

700 kidney transplant recipients were prospectively screened for serological responses (median time of 33 (21-52) days) following 3 primary doses of a SARS-CoV2 vaccine. All vaccine doses were received post-transplant, and all 3 rd doses were BNT162b2. All participants had serological testing performed post-2 nd vaccination at a median time of 34 (IQR 26-46) days following the 2 nd inoculation, and at least once prior to their 1 st dose of vaccine.

Results

366/700 (52.3%) participants were primed with BNT162b2, whilst 334/700 (47.7) had received ChAdOx1. Overall, 139/700 (19.9%) participants had evidence of prior infection. Of 561 infection naïve participants, 263 (46.9%) had no detectable anti-S following 2-doses of vaccine (V2). 134 (23.9%) participants remained seronegative post 3 rd vaccine (V3); 54/291 (18.6%) and 79/270 (29.3%) of participants receiving BNT162b2 and ChAdOx1 respectively, p=0.0029. Median anti-S concentrations were significantly higher post-V3 in patients who had received BNT162b2 compared with ChAdOx1, at 612 (27-234) versus 122 (7.1-1111) BAU/ml respectively, p<0.0001.

Cellular responses were investigated in 30 infection naïve participants at a median time of 35 (24-46) days post-V3. Eighteen of 30 (60.0%) participants had undetectable T-cell responses. There were neither qualitative or quantitative differences in T-cell responses between those patients who received BNT162b2 or ChAdOx1 as their first 2-doses, with 10/16 (62.5%) and 8/14 (57.1%) respectively having undetectable T-cell responses, p=0.77.

Conclusion

A significant proportion of transplant recipients remain seronegative following 3 doses of SARS-CoV-2 vaccines, with anti-S concentrations lower in patients receiving heterologous versus homologous vaccinations.

Article activity feed

  1. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/5979549.

    Main Claim & Relevance:

    Patients that were primed with BNT162b2 for the first two vaccines and received the BNT162b2 booster had higher anti-S concentrations compared to the patients that were primed with ChAdOx1 for the first two vaccines and BNT162b2 booster vaccine. In addition, it was suggested that it might be helpful to consider measuring T-cell response in transplant patients as a possible marker for protection against severe diseases. In the results, it was stated that there was no difference in response between ChAdOx1 and BNT162b2

     

    Are the findings strong, reliable, potentially informative, not informative, or misleading?

    These findings are potentially informative. Although some questions in the methods. Such as, how were the participants picked? or a comparative for mRNA efficacy? More details would be informative.

     

    How might these ideas presented by the main claims further knowledge of the COVID-19 Pandemic?

    With the constant reports of new variants appearing and with that vaccine boosters need to be administered. As such those that are immune vulnerable, like transplant patients, being protected against severe diseases is important.

  2. ScreenIT

    SciScore for 10.1101/2022.01.25.22269778: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study ‘The effect of COVID-19 on Renal and Immunosuppressed patients’, sponsored by Imperial College London, was approved by the Health Research Authority, Research Ethics Committee (Reference: 20/WA/0123)
    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 nucleocapsid protein (anti-NP) using the Abbott Architect SARS-CoV-2 IgG 2 step chemiluminescent immunoassay (CMIA) according to manufacturer’s instructions.
    anti-NP
    suggested: None
    Spike protein antibodies (anti-S IgG) were detected 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 for positivity of 7.1 BAU/ml, to a maximum value of 5680 BAU/ml.
    Anti-S
    suggested: None
    Prior to December 2021, prior infection was determined by the presence of anti-NP or receptor binding domain (RBD) antibodies, using an in-house double binding antigen ELISA (Imperial Hybrid DABA; Imperial College London, London, UK), which detects total RBD antibodies.
    anti-NP or receptor binding domain ( RBD )
    suggested: None
    in-house double binding antigen ELISA
    suggested: None
    Software and Algorithms
    SentencesResources
    Spike protein antibodies (anti-S IgG) were detected 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 9.3.1 (GraphPad Software Inc.
    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:
    Given the relatively small number of patients included in our cellular response analysis, and limitation of assessment of a single functional measure, our conclusions are restricted, but herein we report comparative cellular responses. Therefore, strategies involving multiple doses of heterologous vaccines may still have a role in the mechanism of defence against SARS-CoV-2 infection in transplant recipients. Whilst immunogenicity data may provide useful data to guide clinical efficacy, real world data on the protection afforded to transplant recipients by vaccination, and the comparative impact of the different vaccines, will be key to the strategic planning to protect transplant recipients. Although data show a reduction in vaccine efficacy across the different platforms in transplant recipients, there are no data to suggest clinical outcomes significantly differ between mRNA-based vaccines and ChAdOx1 after two doses in the era where the Delta variant predominated(10). Importantly, whilst the transplant community continues to navigate its way through the pandemic, adaptation of approaches to protect transplant recipients will be necessary, and likely to be reliant on a variety of different methods. Such approaches need to be tailored to the individual patients, specific variants, and infection rates. For patients who have inadequate immune responses to 3-doses of vaccine, alternative immune protection could be better offered from passive immunity, however if repeated vacci...

    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.

    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.

  3. Version published to 10.1101/2022.01.25.22269778v1 on medRxiv