Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial
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Abstract
Symptomatic COVID-19 infection can be prevented by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. A “correlate of protection” is a molecular biomarker to measure how much immunity is needed to fight infection and is key for successful global immunization programs. Gilbert et al . determined that antibodies are the correlate of protection in vaccinated individuals enrolled in the Moderna COVE phase 3 clinical trial (see the Perspective by Openshaw). By measuring binding and neutralizing antibodies against the viral spike protein, the authors found that the levels of both antibodies correlated with the degree of vaccine efficacy. The higher the antibody level, the greater the protection afforded by the messenger RNA (mRNA) vaccine. Antibody levels that predict mRNA vaccine efficacy can therefore be used to guide vaccine regimen modifications and support regulatory approvals for a broader spectrum of the population. —PNK
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SciScore for 10.1101/2021.08.09.21261290: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Trial design and COVID-19 endpoint evaluated for correlates: From July 27, 2020 to October 23, 2020, 30,415 participants were randomized (1:1 ratio) to receive two injections of mRNA-1273 (100 μg) or placebo at Day 1 and at Day 29.9 Correlates were evaluated against the protocol-specified primary endpoint, referred to as “COVID-19”: first occurrence of acute symptomatic COVID-19 with virologically-confirmed SARS-CoV-2 infection in participants with no evidence of previous SARS-CoV-2 infection. Blinding 9 Correlates analyses included COVID-19 endpoints diagnosed during two time periods: “intercurrent endpoints” starting 7 days … SciScore for 10.1101/2021.08.09.21261290: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Trial design and COVID-19 endpoint evaluated for correlates: From July 27, 2020 to October 23, 2020, 30,415 participants were randomized (1:1 ratio) to receive two injections of mRNA-1273 (100 μg) or placebo at Day 1 and at Day 29.9 Correlates were evaluated against the protocol-specified primary endpoint, referred to as “COVID-19”: first occurrence of acute symptomatic COVID-19 with virologically-confirmed SARS-CoV-2 infection in participants with no evidence of previous SARS-CoV-2 infection. Blinding 9 Correlates analyses included COVID-19 endpoints diagnosed during two time periods: “intercurrent endpoints” starting 7 days post Day 29 visit through 6 days post Day 57 visit and “post Day 57 endpoints” starting 7 days post Day 57 visit and any time during follow-up while participants were still blinded to randomization assignment (Figure S1). Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:With the caveats of different study endpoints/hosts, the COVE results are also consistent with results on Spike IgG and neutralizing antibody titers as correlates of protection against SARS-CoV-2 replication in mRNA-1273-vaccinated rhesus macaques. For instance, all macaques with Spike IgG > 336 IU/ml at 4 weeks post second dose were protected from >10,000 subgenomic RNA copies/ml in bronchoalveolar lavages,30 and in COVE, Day 57 Spike IgG of 336 IU/ml corresponded to 90% vaccine efficacy against COVID-19 (Figure S22). Together with evidence from other studies, the current results support that neutralization titer is a potential surrogate marker for mRNA-1273 vaccination against COVID-19 that can be considered as a primary endpoint for basing certain accelerated approval decisions. The total body of evidence may support an immunogenicity non-inferiority approach to bridging vaccine efficacy of refined or novel mRNA vaccines, which has been proposed for adding vaccine spike variants and boosters.47 One open question challenging this approach is whether titers to different strains have different relationships with vaccine efficacy. A more challenging objective is bridging vaccine efficacy of new candidate vaccines in different platforms from mRNA. When correlates results are available from several phase 3 vaccine efficacy trials of different vaccine platforms, it will be possible to conduct validation analyses of how well an antibody marker can be used to predict vaccine effica...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04470427 Active, not recruiting A Study to Evaluate Efficacy, Safety, and Immunogenicity of … 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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