Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
The COVID-19 pandemic has had an unprecedented impact. Although several vaccines have received emergency use authorization, demand has created enormous logistical challenges—including supply, access, and distribution—that justify research for alternative strategies. Phage are viruses that only infect bacteria and can be safely administered to humans. Here, as a proof-of-concept study, we demonstrate that aerosol vaccination with lung-targeted phage particles displaying short SARS-CoV-2 S protein epitopes and subcutaneous vaccination with targeted AAVP particles carrying the entire S protein gene both elicit systemic and specific immune responses in immunocompetent mice. Given their unique attributes, including sturdiness, simple-to-engineer platform, cost-effectiveness for rapid large-scale production, and stability at room temperature, these phage-based approaches may become attractive tools for COVID-19 vaccine development.
Article activity feed
-
-
SciScore for 10.1101/2021.03.15.435496: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The Institutional Animal Care and Use Committee (IACUC) from the Rutgers Cancer Institute of New Jersey approved all animal experiments. Randomization Littermates were randomly assigned to experimental groups. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Following three washes with PBS and PBS containing 0.1% of Tween 20, bound antibodies were detected with an anti-mouse IgG HRP-conjugated (Jackson ImmunoResearch) at optical density (OD) at 450 nm. anti-mouse IgGsuggested: NoneCommercially available polyclonal IgG anti-Spike protein antibody (Thermo Fisher, MA5-35949) or … SciScore for 10.1101/2021.03.15.435496: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The Institutional Animal Care and Use Committee (IACUC) from the Rutgers Cancer Institute of New Jersey approved all animal experiments. Randomization Littermates were randomly assigned to experimental groups. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Following three washes with PBS and PBS containing 0.1% of Tween 20, bound antibodies were detected with an anti-mouse IgG HRP-conjugated (Jackson ImmunoResearch) at optical density (OD) at 450 nm. anti-mouse IgGsuggested: NoneCommercially available polyclonal IgG anti-Spike protein antibody (Thermo Fisher, MA5-35949) or anti-fd bacteriophage antibody (Sigma Aldrich) served as positive controls. anti-Spike proteinsuggested: Noneanti-fd bacteriophagesuggested: NoneExperimental Models: Organisms/Strains Sentences Resources Animals: Four-to-six-week-old Swiss Webster and BALB/c mice were purchased from the Jackson Laboratory (Sacramento, CA) and were housed in specific pathogen and opportunist free (SOPF) rooms with controlled temperature (20 ± 2°C), humidity (50 ± 10%), light cycle (light, 7:00-19:00; dark, 19:00 – 7:00), and access to food and water ad libitum at the research animal facilities of the Rutgers Cancer Institute of New Jersey. BALB/csuggested: NoneSoftware and Algorithms Sentences Resources P-7734T13) were added to the 5’ or 3’ ends, respectively, to the modified synthetic SARS-CoV-2 S gene to produce a 3.909 kb modified SARS-CoV-2 S gene that was subcloned into the EcoRI and SalI restriction sites of pUC57/AmpR at GeneWiz. GeneWizsuggested: (GENEWIZ, RRID:SCR_003177)Positive clones were verified by EcoRI restriction mapping, confirmed with overlapping sense and antisense primers by Sanger sequencing (SeqStudio, Thermo Fisher Scientific) using the BigDye Terminator v.3.1 Cycle Sequencing and XTerminator Purification kits (Applied Biosystems, Thermo Fisher Scientific) and analyzed using SnapGene software (GSL Biotech, San Diego, CA). SnapGenesuggested: (SnapGene, RRID:SCR_015052)Statistical Analysis: Differences between groups were tested for statistical significance with Student’s t-test or analysis of variance (one-way or two-way ANOVA) using GraphPad Prism 8. GraphPad Prismsuggested: (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.
-
