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

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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.

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  1. 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 …

  2. 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 …