Determinants of SARS-CoV-2 anti-spike antibody levels following BNT162b2 vaccination: cross-sectional analysis of 6,000 SIREN study participants
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Background
Understanding immunological responses to SARS-CoV-2 vaccinations is integral to the management of SARS-CoV-2. We aimed to investigate determinants of antibody response to the BNT162b2 vaccine.
Methods
A cross-sectional analysis of anti-spike binding antibodies in serum samples from healthcare workers after one or two doses. Post-vaccination interval was restricted to ≥21 days after dose 1, ≥14 days after dose 2. The primary outcome was anti-S titres with explanatory variables dose, previous infection, dosing interval, age, ethnicity, and comorbidities. Multivariable linear regression was also conducted.
Results
Participants (n=5,871) included 3,989 post-dose 1, 1,882 post-dose 2. In SARS-CoV-2 infection naïve, 99.65% seroconverted after dose 1 and >99.9% seroconverted after dose 2. Geometric mean anti-S titre in the naïve cohort was 75.48 Binding Antibody Units/ml after dose 1, 7,049 BAU/ml after dose 2. Anti-S titres were higher in those with previous infection (2,111 BAU/ml post-dose 1, 16,052 BAU/ml post-dose 2), and increased with time between infection and vaccination: 3 months 1,970 (1,506-2,579) vs 9 months; 13,759 (8,097-23,379). Longer dosing intervals increased antibody response post-dose 2: 11-fold higher with a longer interval (>10 weeks) than those with shorter intervals, across all age-groups. Younger participants had higher mean titres (>2.2-fold higher). Multivariable regression modelling corroborated the above associations, and also found higher titres associated with being female or from an ethnic minority but lower titres among immunocompromised participants.
Conclusion
The number of antigen exposures and timing between vaccinations plays a significant role in the magnitude of the post-vaccination antibody response, with implications for long-term protection and post-booster antibody responses.
Article activity feed
-
SciScore for 10.1101/2022.04.21.22274025: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethics: Ethics approval was granted on 22 May 2020 under IRAS ID 284460, Berkshire Research Ethics Committee Approval by HRA and Health and Care Research Wales. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources In brief, eligible participants had submitted an enrolment sample (baseline sample) that had been tested using the Roche Elecsys quantitative SARS-CoV-2 anti-spike (S) and semi-quantitative anti-nucleocapsid (N) antibody assays and submitted this after their first or second COVID-19 vaccination, or were anti-N positive and submitted the sample before vaccination. anti-spi…SciScore for 10.1101/2022.04.21.22274025: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethics: Ethics approval was granted on 22 May 2020 under IRAS ID 284460, Berkshire Research Ethics Committee Approval by HRA and Health and Care Research Wales. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources In brief, eligible participants had submitted an enrolment sample (baseline sample) that had been tested using the Roche Elecsys quantitative SARS-CoV-2 anti-spike (S) and semi-quantitative anti-nucleocapsid (N) antibody assays and submitted this after their first or second COVID-19 vaccination, or were anti-N positive and submitted the sample before vaccination. anti-spike ( S )suggested: Noneanti-nucleocapsid ( Nsuggested: Noneanti-Nsuggested: NoneOutcomes: The primary outcome was anti-S titre using the Roche Elecsys anti-spike (ACOV2 S) assay which specifically targets anti-RBD antibodies, as described elsewhere4,16. anti-Ssuggested: Noneanti-RBDsuggested: NoneSamples were considered positive for anti-nucleocapsid and anti-spike antibodies if the results were ≥1.0 COI and ≥0.8 U/ml, respectively. anti-spikesuggested: NoneThe Roche Elecsys anti-nucleocapsid assay is semi-quantitative, as described elsewhere17, with the presence of anti-nucleocapsid antibodies used as a proxy for probable previous infection in the absence of a previous PCR positive. anti-nucleocapsidsuggested: NoneSoftware and Algorithms Sentences Resources Statistical analysis: All statistics were performed on log transformed anti-spike antibody values (in BAU/ml), unless otherwise stated, using R (version 4.0.2), with regression analysis performed in STATA (version 14.2). STATAsuggested: (Stata, RRID:SCR_012763)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title ISRCTN11041050 NA NA 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.
-
