Immunogenicity and Safety of Beta-Adjuvanted Recombinant Booster Vaccine

Article activity feed

1. Version published to 10.1056/nejmc2206711

   Jul 28, 2022
2. 

   ScreenIT

   May 30, 2022

   SciScore for 10.1101/2022.05.25.22274904: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	IRB: It was approved by the “CPP Ile de France III” Ethics Committee and the French Health Products Safety Agency (ANSM).
   Sex as a biological variable	not detected.
   Randomization	Study design: We conducted a randomized, single-blinded, multicenter trial across 11 centers in France.
   Blinding	The central laboratories performing the antibody analyses were also blinded to limit measurement bias.
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   The main other prespecified immunological endpoints were the rate of increase between day 0 and day 15 in neutralizing antibody titers against SARS-CoV-2 Wuhan (D614) and variants Beta, Delta and …

   SciScore for 10.1101/2022.05.25.22274904: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	IRB: It was approved by the “CPP Ile de France III” Ethics Committee and the French Health Products Safety Agency (ANSM).
   Sex as a biological variable	not detected.
   Randomization	Study design: We conducted a randomized, single-blinded, multicenter trial across 11 centers in France.
   Blinding	The central laboratories performing the antibody analyses were also blinded to limit measurement bias.
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   The main other prespecified immunological endpoints were the rate of increase between day 0 and day 15 in neutralizing antibody titers against SARS-CoV-2 Wuhan (D614) and variants Beta, Delta and Omicron BA.1, geometric mean of anti-Spike IgG levels (expressed as BAU/mL) and IFNγ and IL-2 secreting CD4+ T-cells after stimulation with Spike peptides derived from wild-type SARS-CoV-2 or Omicron variant in each randomized group.	SARS-CoV-2 Wuhan ( D614 suggested: None anti-Spike IgG suggested: None
   As no data was available on the BNT162b2 vaccine, the sample size calculation was based on published data on the mRNA-1273 vaccine in which an increase rate of neutralizing antibody titer of 23 against ancestral SARS-CoV-2 (D614G) and 32 for the B.1.351 variant after mRNA-1273 boost was described.	D614G suggested: None
   For each group, the anti-SARS-CoV-2 IgG antibody titers directed against the S1 domain of the spike protein and the neutralizing antibody titers measured by a microneutralization technique against Wuhan strain (D614) and variants (B.1.351, Delta, Omicron BA.1) measured at day 0, day 15 were described as geometric means with two-sided 95% confidence intervals (95% CI).	anti-SARS-CoV-2 IgG suggested: None
   Experimental Models: Cell Lines
   Sentences	Resources
   , TMPRSS2-expressing VeroE6 cells and relies on cytopathic effect (CPE) identification at 5 days post-infection.	VeroE6 suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
   Software and Algorithms
   Sentences	Resources
   The statistical analysis was conducted using SAS software version 9.4 (SAS Institute, Inc.	SAS suggested: (SASqPCR, RRID:SCR_003056) SAS Institute suggested: (Statistical Analysis System, RRID:SCR_008567)
   R freeware (version 3.6.3) and GraphPad Prism software (version 9.2.0, San Diego, California USA) were used for the graphs.	GraphPad Prism suggested: (GraphPad Prism, RRID:SCR_002798)

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   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).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   This study has some limitations. Compared to the at-risk population for severe forms of SARS-CoV-2 infection, the study population was younger and included a smaller percentage of people ≥65 years than previously planned. Indeed, by the time the study was started, the elderly population had already received a third dose. Another limitation is the priming with a unique vaccine. The primary endpoint was based on an increase in neutralizing antibodies against the Wuhan (D614) and B.1.351 (Beta) strains, which are variants of SARS-CoV-2 that no longer circulate. However neutralizing antibodies against more recent variants were also evidenced. Despite these limitations, our study is the first to report immunization and reactogenicity data on the heterologous boost with an adjuvanted recombinant protein vaccine containing a variant of concern different from the one present at the priming. The higher neutralizing response elicited by the vaccine containing the Beta Spike protein will need further investigations to understand the mechanisms underlying these results. Of interest, this higher immunogenicity was not associated with higher reactogenicity. However, the observed higher immunogenicity should be interpreted with caution, as the relationship between antibody levels at 15 days and the long-term protection remains to be fully characterized. These results, which address the possibility of combining different vaccines for priming and boosting, are important for vaccination campai...

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

   Identifier	Status	Title
   NCT05124171	Active, not recruiting	Immunogenicity and Reactogenicity Following a Booster Dose o…

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   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.
   • Thank you for including a protocol registration statement.

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   Results from scite Reference Check: We found no unreliable references.

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   Read the original source
3. 

   Version published to 10.1101/2022.05.25.22274904 on medRxiv

   May 27, 2022