Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial

Article activity feed

1. Version published to 10.1038/s41591-022-01739-w

   Mar 3, 2022
2. 

   ScreenIT

   Oct 4, 2021

   SciScore for 10.1101/2021.09.29.21264089: (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	Trial participants: Eligible participants in Part A were male or female, 18 years of age or older at screening and in good general health according to the investigator.
   Randomization	Study design: This phase 2 study (NCT04405076) enrolled 600 participants to receive placebo, or 50 or 100 µg of mRNA-1273 (randomized 1:1:1; Figure 1A) in two cohorts of participants ≥18 to <55 years old (Cohort 1) and participants ≥ 55 years old (Cohort 2) in the observer-blind and placebo-controlled part of the study (Part A; Figure 1).
   Blinding	The randomization was performed in a blinded manner using a centralized Interactive Response Technology.
   Power Analysis	Statistical…

   SciScore for 10.1101/2021.09.29.21264089: (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	Trial participants: Eligible participants in Part A were male or female, 18 years of age or older at screening and in good general health according to the investigator.
   Randomization	Study design: This phase 2 study (NCT04405076) enrolled 600 participants to receive placebo, or 50 or 100 µg of mRNA-1273 (randomized 1:1:1; Figure 1A) in two cohorts of participants ≥18 to <55 years old (Cohort 1) and participants ≥ 55 years old (Cohort 2) in the observer-blind and placebo-controlled part of the study (Part A; Figure 1).
   Blinding	The randomization was performed in a blinded manner using a centralized Interactive Response Technology.
   Power Analysis	Statistical analyses: The results for the two groups that received a booster injection after a primary series of two doses of 50 µg or 100 µg of mRNA-1273 were expected to be similar and have been combined for the immunogenicity analysis to increase the statistical power for comparisons to the historical control from the phase 3 COVE trial.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   29 The virus was applied to transduced 293T cells expressing high levels of ACE2 (293T/ACE2 cells), with or without pre-incubation with antibodies (control antibodies or serum samples); the presence of neutralizing antibodies reduced infection and resulted in lower RLUs.	ACE2 suggested: None
   Meso-Scale Discovery (MSD) 3-PLEX assay: This quantitative electrochemiluminescence (ECL) method is an indirect binding ECL method designed to detect SARS-CoV-2 antibodies [SARS-CoV-2 Spike (S; Wuhan-Hu-1 isolate including D614G), nucleocapsid (N), and receptor binding domain (RBD) antibodies] in human serum.	, nucleocapsid ( N) , and receptor binding domain ( RBD ) suggested: None
   Serum containing the SARS-CoV-2 IgG antibody was added to the plates.	SARS-CoV-2 IgG suggested: None
   Bound antigen-antibody complex was detected using purified goat anti-human IgG horseradish peroxidase conjugate.	anti-human IgG suggested: None
   The intensity of the color was directly proportional to the IgG antibody concentration.	IgG suggested: None
   Quantitation of the human IgG antibody to SARS-CoV-2, or antibody concentration (AU/mL), was determined by interpolation from a standard curve analyzed on each assay plate.	SARS-CoV-2 suggested: None
   Experimental Models: Cell Lines
   Sentences	Resources
   29 The virus was applied to transduced 293T cells expressing high levels of ACE2 (293T/ACE2 cells), with or without pre-incubation with antibodies (control antibodies or serum samples); the presence of neutralizing antibodies reduced infection and resulted in lower RLUs.	293T suggested: None 293T/ACE2 suggested: RRID:CVCL_YZ65)

   ---

   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:

   There are several limitations to the results of this study. This study was designed to assess the safety and immune response of a third dose of mRNA-1273 administered at least 6 months after the initial priming series. While the optimal timing of a third dose has not been established, the data from this trial provides important information to address the need for third booster dose in case of waning vaccine effectiveness. Although neutralizing antibody responses have been correlated to reduction of risk for breakthrough COVID-19 disease,37 a threshold of protection has not been defined for the Wuhan-1 or Delta variants. Also, this study did not examine variant-specific booster vaccines or immune responses to variants of concern other than for Delta. Finally, this study showed an immune memory antibody response to the spike protein of SARS-CoV-2 but did not examine T cell memory or quantify B memory cells. While the data supporting the timing of when booster doses of mRNA vaccine against SARS-CoV-2 should be administered is still evolving, the results from this study provide evidence that a third dose of mRNA-1273 administered at least 6 months after the primary series is safe and effective in inducing a booster response, as indicated by the statistically significantly higher antibody titers observed after the 50 µg booster dose as compared to after the second priming dose of 100 µg of mRNA-1273. A booster dose of mRNA-1273 has the potential for establishing durable vaccine ef...

   ---

   Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
   

   Identifier	Status	Title
   NCT04405076	Active, not recruiting	Dose-Confirmation Study to Evaluate the Safety, Reactogenici…

   ---

   Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

   ---

   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.

   ---

   Read the original source
3. 

   Version published to 10.1101/2021.09.29.21264089v1 on medRxiv

   Oct 1, 2021