Intranasal Immunization with a Proteosome-Adjuvanted SARS-CoV2 Spike Protein-Based Vaccine is Immunogenic and Efficacious in Mice & Hamsters
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Abstract
With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine.
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SciScore for 10.1101/2022.03.02.482651: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All procedures performed on animals in this study were in accordance with regulations and guidelines reviewed and approved in animal use protocol 2020.06 & 2020.10 by the NRC Human Health Therapeutics Animal Care Committee. Sex as a biological variable Animals and Virus: Female BALB/c mice (8-12 weeks old) and both male and female golden Syrian hamsters (81-90 g) were obtained from Charles River Laboratories (Saint-Constant, Canada). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Bound IgA Abs were detected spectrophotometrically at 450 nm, and IgA antibody titers were determined … SciScore for 10.1101/2022.03.02.482651: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All procedures performed on animals in this study were in accordance with regulations and guidelines reviewed and approved in animal use protocol 2020.06 & 2020.10 by the NRC Human Health Therapeutics Animal Care Committee. Sex as a biological variable Animals and Virus: Female BALB/c mice (8-12 weeks old) and both male and female golden Syrian hamsters (81-90 g) were obtained from Charles River Laboratories (Saint-Constant, Canada). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Bound IgA Abs were detected spectrophotometrically at 450 nm, and IgA antibody titers were determined as above for IgG. IgAsuggested: NoneExperimental Models: Cell Lines Sentences Resources Indicated dilutions of mouse/hamster serum were incubated with 250 ng of biotinylated Spike and 1×105 Vero E6 cells (ATCC® CRL-1586™) in the presence of PBS, 0.05% sodium azide (Thermo Fisher Scientific) and 1% bovine serum albumin (BSA; Rockland, Philadelphia, PA, USA) within a 96-well V-bottom plate (Nunc™, Thermo Fisher Scientific) for 1 hour at 4 °C, while protected from light. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Animals and Virus: Female BALB/c mice (8-12 weeks old) and both male and female golden Syrian hamsters (81-90 g) were obtained from Charles River Laboratories (Saint-Constant, Canada). BALB/csuggested: NoneThe ancestral reference strain of SARS-CoV-2 (isolate Canada/ON/VIDO-01/2020 obtained from the National Microbiology Lab, Winnipeg, Canada) was propagated and quantified on Vero E6 cells. Canada/ON/VIDO-01/2020suggested: NoneRecombinant DNA Sentences Resources Constructs were then cloned into the pTT241 plasmid that did not encode C-terminal FLAG/His affinity tags. pTT241suggested: NoneSoftware and Algorithms Sentences Resources After another wash, the cells were fixed using CytoFix™ (Becton Dickinson, Franklin Lakes, NJ, USA) and resuspended in wash buffer + 5mM EDTA for acquisition on an LSR Fortessa™ (Becton Dickinson). CytoFix™suggested: NoneStatistical analysis: Data were analyzed using GraphPad Prism® version 9 (GraphPad Software, San Diego, CA, USA). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)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: 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: No clinical trial numbers were referenced.
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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