Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection
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Abstract
Background
Although 6 COVID-19 vaccines have been approved by the World Health Organisation as of 16 th June 2021, global supply remains limited. An understanding of the immune response associated with protection could facilitate rapid licensure of new vaccines.
Methods
Data from a randomised efficacy trial of ChAdOx1 nCoV-19 (AZD1222) vaccine in the UK was analysed to determine the antibody levels associated with protection against SARS-CoV-2. Anti-spike and anti-RBD IgG by multiplex immunoassay, pseudovirus and live neutralising antibody at 28 days after the second dose were measured in infected and non-infected vaccine recipients. Weighted generalised additive models for binary data were applied to symptomatic and asymptomatic SARS-CoV-2 infection data from ChAdOx1 nCoV-19 recipients. Cubic spline smoothed log antibody levels, and weights were applied to account for potential selection bias in sample processing. Models were adjusted for baseline risk of exposure to SARS-CoV-2 infection.
Results
Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Vaccine efficacy of 80% against primary symptomatic COVID-19 was achieved with an antibody level of 40923 (95% CI: 16748, 125017) and 63383 (95% CI: 16903, not computed (NC)) for anti-spike and anti-RBD, and 185 (95% CI: NC, NC) and 247 (95% CI: 101, NC) for pseudo- and live-neutralisation assays respectively. Antibody responses did not correlate with overall protection against asymptomatic infection.
Conclusions
Correlates of protection can be used to bridge to new populations using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where large efficacy trials cannot be conducted. More work is needed to assess correlates for emerging variants.
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SciScore for 10.1101/2021.06.21.21258528: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: All endpoints were evaluated by a blinded independent clinical review committee. Sex as a biological variable not detected. Randomization Study description: The data included in this analysis comes from participants enrolled in COV002, a phase 2/3 randomised single blind vaccine efficacy trial conducted across 19 sites in the UK. Blinding Study description: The data included in this analysis comes from participants enrolled in COV002, a phase 2/3 randomised single blind vaccine efficacy trial conducted across 19 sites in the UK. Power Analysis not detected. Cell Line Authentication Authentication: The data from non-cases consisted mainly of the samples processed for the initial application for … SciScore for 10.1101/2021.06.21.21258528: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: All endpoints were evaluated by a blinded independent clinical review committee. Sex as a biological variable not detected. Randomization Study description: The data included in this analysis comes from participants enrolled in COV002, a phase 2/3 randomised single blind vaccine efficacy trial conducted across 19 sites in the UK. Blinding Study description: The data included in this analysis comes from participants enrolled in COV002, a phase 2/3 randomised single blind vaccine efficacy trial conducted across 19 sites in the UK. Power Analysis not detected. Cell Line Authentication Authentication: The data from non-cases consisted mainly of the samples processed for the initial application for emergency use which needed 15% of samples included in the efficacy cohort to be processed on validated assays. Table 2: Resources
Software and Algorithms Sentences Resources The immune correlates SAP leant heavily on the methods proposed in the publicly available SAP by the Coronavirus Prevention Network (CoVPN) Biostatistics Team.27 Biostatisticssuggested: (BWH Biostatistics Center, RRID:SCR_009680)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:Limitations: These analyses are based on cases of COVID-19 detected in a mainly white population in the UK, which were mostly due to B.1.177 and B.1.1.7 variants. In settings where these are not the dominant variants causing disease, or where neutralisation assays use different strains of the virus, the modelled relationships between immune markers and disease outcomes shown here may not apply. Furthermore, these analyses have been conducted on samples taken after 2 doses of ChAdOx1 nCoV-19 and might not apply to protection afforded by a single dose of the same vaccine or other COVID-19 vaccines. The potential role of T cells and interaction between humoral and cellular immunity has not been evaluated in this study. Conclusions: Correlates of protection can be used to bridge to new populations and new vaccines using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where efficacy data is unavailable.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04400838 Active, not recruiting Investigating a Vaccine Against COVID-19 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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