Immune response to 2-dose BNT162b2 vaccination and risk of SARS-CoV-2 breakthrough infection: The Shieldvacc-2 study
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Abstract
It is uncertain to which extent antibody and T-cell responses after vaccination against SARS-CoV-2 are associated with reduced risk of breakthrough infection and whether their measurement enhances risk prediction. We conducted a phase-4 open-label clinical trial in the pre-omicron era, enrolling 2,760 individuals aged ≥16 years 35±8 days after having received the second dose of BNT162b2 (baseline 15-21 May 2021). Over a median 5.9-month of follow-up, we identified incident SARS-CoV-2 breakthrough infections using weekly antigen tests, a confirmatory PCR test, and/or serological evidence for incident infection. We quantified relative risks adjusted for age, sex, and prior SARS-CoV-2 infection for different immunological parameters and assessed improvements in risk discrimination. In contrast to the T-cell response, higher plasma levels of binding antibodies and antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Furthermore, assessment of anti-spike IgG levels enhanced prediction of breakthrough infection and may therefore be a suitable measurable correlate of protection in practice.
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SciScore for 10.1101/2022.04.19.22273872: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Written informed consent was provided by study participants or – if appropriate – by the individual’s legal representative or custodial.
IRB: The study was approved by the ethics committee of the Medical University of Innsbruck (no. 1168/2021) and has been registered at the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT number: 2021-002030-16).Sex as a biological variable not detected. Randomization Furthermore, to evaluate cellular immune responses, in a random subgroup of 929 participants, additional blood samples were collected in S-Monovette tubes (Sarstedt, Nümbrecht, Germany Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies S… SciScore for 10.1101/2022.04.19.22273872: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Written informed consent was provided by study participants or – if appropriate – by the individual’s legal representative or custodial.
IRB: The study was approved by the ethics committee of the Medical University of Innsbruck (no. 1168/2021) and has been registered at the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT number: 2021-002030-16).Sex as a biological variable not detected. Randomization Furthermore, to evaluate cellular immune responses, in a random subgroup of 929 participants, additional blood samples were collected in S-Monovette tubes (Sarstedt, Nümbrecht, Germany Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources In brief, to assess antibody responses, plasma samples were collected in S-Monovette tubes (Sarstedt, Nümbrecht, Germany) containing ethylenediaminetetraacetic acid anticoagulant (EDTA KE/9 mL) and were analyzed with three distinct commercially available serological tests: (i) the Abbott SARS-CoV-2 IgG II Quant chemiluminescent microparticle immunoassay on the Alinity i instrument (Abbott Ireland, Sligo, Ireland) to measure anti-S IgG; (ii) the Roche Elecsys Anti-SARS-CoV-2 electrochemiluminescent immunoassay on the Cobas e411 analyzer (Roche, Mannheim, Germany) to measure anti-N Ig; and (iii) the TECO anti-S IgGsuggested: Noneanti-N Igsuggested: NoneSoftware and Algorithms Sentences Resources In brief, to assess antibody responses, plasma samples were collected in S-Monovette tubes (Sarstedt, Nümbrecht, Germany) containing ethylenediaminetetraacetic acid anticoagulant (EDTA KE/9 mL) and were analyzed with three distinct commercially available serological tests: (i) the Abbott SARS-CoV-2 IgG II Quant chemiluminescent microparticle immunoassay on the Alinity i instrument (Abbott Ireland, Sligo, Ireland) to measure anti-S IgG; (ii) the Roche Elecsys Anti-SARS-CoV-2 electrochemiluminescent immunoassay on the Cobas e411 analyzer (Roche, Mannheim, Germany) to measure anti-N Ig; and (iii) the TECO Abbottsuggested: NoneThe ratios of IFN-γ values from SARS-CoV-2 specific stimulation and the unstimulated control (Nil) was determined as the SI. SARS-CoV-2suggested: (Active Motif Cat# 91351, RRID:AB_2847848)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:Our study also has limitations. First, cellular immune parameters were available only for a (random) subgroup of participants, thereby limiting statistical power. Second, the QuantiFERON SARS-CoV-2 assay was limited to measure the Interferon-Gamma (IFN-γ) production after stimulation with CD4 and combined CD4 and CD8 peptide pools, therefore a detailed characterization of T-cell response with respect of the source of IFN-γ (CD4 or CD8 T-cells), phenotypical and further functional analysis of T-cells is missing. Third, the proportion of participants with a prior SARS-CoV-2 infection was relatively high (25.8%) and is likely due to high interest to participate in the study. Ascertainment of prior infection was of high quality as it was performed by trained study staff and was confirmed by a positive anti-N Ig measurement in 92% of cases. Fourth, we conducted our study during a phase in which Delta was the predominant variant of concern and associations of immunological parameters with Omicron may be weaker. Finally, these analyses have been conducted on samples taken after two doses of BNT162b2 and might not apply to other coronavirus disease 2019 (COVID-19) vaccines or to people that received a third doses of BNT162b2. In conclusion, in contrast to the T-cell response, higher plasma levels of binding and neutralizing antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Assessment of anti-S IgG levels enhances prediction of...
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.
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