Immune Correlates Analysis of a Single Ad26.COV2.S Dose in the ENSEMBLE COVID-19 Vaccine Efficacy Clinical Trial
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Abstract
Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.
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SciScore for 10.1101/2022.04.06.22272763: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Neutralizing antibody activity was measured at Monogram in a formally validated assay (detailed in Huang et al.28) that utilized lentiviral particles pseudotyped with full-length SARS-CoV-2 Spike protein. SARS-CoV-2 Spike protein .suggested: NoneCase-cohort set included in the correlates analyses: A case-cohort36 sampling design was used to randomly sample participants for D1, D29 antibody marker measurements. D1suggested: (GenWay Biotech Inc. Cat# GWB-1D1D29, RRID:AB_10511088)D29suggested: NoneSoftware and Algorithms Sentences Resources Further differences between the moderate to severe-critical … SciScore for 10.1101/2022.04.06.22272763: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Neutralizing antibody activity was measured at Monogram in a formally validated assay (detailed in Huang et al.28) that utilized lentiviral particles pseudotyped with full-length SARS-CoV-2 Spike protein. SARS-CoV-2 Spike protein .suggested: NoneCase-cohort set included in the correlates analyses: A case-cohort36 sampling design was used to randomly sample participants for D1, D29 antibody marker measurements. D1suggested: (GenWay Biotech Inc. Cat# GWB-1D1D29, RRID:AB_10511088)D29suggested: NoneSoftware and Algorithms Sentences Resources Further differences between the moderate to severe-critical COVID-19 endpoint for the correlates analysis vs. that for the primary analysis are: the correlates analysis counted endpoints starting both ≥ 1 day post-D29 and ≥ 28 days post-vaccination and RT-PCR positivity of a nasal swab for SARS-CoV-2 was determined at a local laboratory (with or without central confirmation), whereas the primary analysis counted endpoints starting ≥ 28 days post-vaccination and all participants whose nasal swabs tested RT-PCR+ for SARS-CoV-2 at a local laboratory must have also had a respiratory tract sample confirmed as SARS-CoV-2 positive at a central laboratory using the m-2000 SARS-CoV-2 real-time RT-PCR assay (Abbott). Abbottsuggested: (Abbott, RRID:SCR_010477)Results from OddPub: Thank you for sharing your code.
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 NCT04505722 Active, not recruiting A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Medi… 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.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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