Sterilizing Immunity against SARS‐CoV‐2 Infection in Mice by a Single‐Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist‐Adjuvanted Recombinant Spike Protein Vaccine**
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- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
The search for vaccines that protect from severe morbidity and mortality because of infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus that causes coronavirus disease 2019 (COVID‐19) is a race against the clock and the virus. Here we describe an amphiphilic imidazoquinoline (IMDQ‐PEG‐CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol‐poly(ethylene glycol) macromolecular amphiphile. It is water‐soluble and exhibits massive translocation to lymph nodes upon local administration through binding to albumin, affording localized innate immune activation and reduction in systemic inflammation. The adjuvanticity of IMDQ‐PEG‐CHOL was validated in a licensed vaccine setting (quadrivalent influenza vaccine) and an experimental trimeric recombinant SARS‐CoV‐2 spike protein vaccine, showing robust IgG2a and IgG1 antibody titers in mice that could neutralize viral infection in vitro and in vivo in a mouse model.
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Yang Shi
Review 1: "Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Modified Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine"
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Yang Shi
Review of "Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Modified Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine"
Reviewer: Yang Shi (Aachen University) | 📘📘📘📘📘
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SciScore for 10.1101/2020.10.23.344085: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Mice, Cell lines and reagents: 6-8 weeks old female BALB/c mice were obtained from Charles River Laboratories, MA and were housed in a specified pathogen-free facility at Icahn school of medicine at Mount Sinai, with food and water ad libitum, adhering to the guidelines from Institutional Animal Care and Use Committee. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mice, Cell lines and reagents: 6-8 weeks old female BALB/c mice were obtained from Charles River Laboratories, MA and were housed in a specified pathogen-free facility at Icahn school of medicine at Mount Sinai, with food and water ad … SciScore for 10.1101/2020.10.23.344085: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Mice, Cell lines and reagents: 6-8 weeks old female BALB/c mice were obtained from Charles River Laboratories, MA and were housed in a specified pathogen-free facility at Icahn school of medicine at Mount Sinai, with food and water ad libitum, adhering to the guidelines from Institutional Animal Care and Use Committee. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mice, Cell lines and reagents: 6-8 weeks old female BALB/c mice were obtained from Charles River Laboratories, MA and were housed in a specified pathogen-free facility at Icahn school of medicine at Mount Sinai, with food and water ad libitum, adhering to the guidelines from Institutional Animal Care and Use Committee. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After 72 hours of incubation at 37°C, 5% CO2, the plates were fixed in 4% formaldehyde, followed by immune-staining of infected cells with anti-mouse SARS-CoV-2 nucleoprotein and anti-mouse SARS-CoV-2 spike monoclonal antibodies. anti-mouse SARS-CoV-2 nucleoproteinsuggested: Noneanti-mouse SARS-CoV-2suggested: NoneAfter incubation in primary antibodies, HRP-conjugated anti-mouse secondary antibody was added for 1 hour. anti-mousesuggested: NoneIsolated lymph nodes were collected in ice cold PBS, smashed through 70 μm cell strainers, washed with PBS and stained for 30min at 4°C with following primary labeled antibodies: CD3, CD20, CD11c, MHCII, CD86, CD40. CD3suggested: NoneCD20suggested: NoneCD11csuggested: NoneCD86suggested: NoneCD40suggested: NoneExperimental Models: Cell Lines Sentences Resources Both cells were maintained in Dulbecco’s Modified Eagle’s Medium supplemented with 10% Fetal bovine serum (FBS) and additionally with 1% non-essential amino acids for Vero-E6 cells. Vero-E6suggested: NoneMurine RAW blue 264.7 macrophages were cultured in DMEM medium supplemented with 10 % heat-inactivated FBS, antibiotics (50 units/mL penicillin and 50 μg/mL streptomycin), 2 mM L-glutamine and 0.01 % Zeocin. RAW blue 264.7suggested: NoneFor IVR-180, MDCK cells were incubated with the lung homogenate dilutions for 1 hour at 37°C, 5% CO2 and then overlaid with a mixture of 2% oxoid agar and 2X minimal essential medium (MEM) supplemented with 1% diethyl-aminoethyl (DEAE)-dextran and 1 μg/ml MDCKsuggested: NoneExperimental Models: Organisms/Strains Sentences Resources In order to make SARS-CoV-2 Spike-vaccinated BALB/c mice susceptible to challenge with wild type SARS-CoV-2 virus, airway expression of human ACE-2, the receptor for SARS-CoV-2, was obtained by intranasal transduction of mice with 2.5×108 PFU of adenovirus expressing h-ACE-2 (Ad5-hACE2), 4.5-weeks post-vaccination as described in (28). BALB/csuggested: NoneAnalysis of in vivo lymphatic drainage: 20 μL (1 mg/mL in PBS) of Cyanine5-PEG-CHOL or Cyanine5-PEG were injected into the footpad of female C57BL/6 WT mice. C57BL/6suggested: NoneSoftware and Algorithms Sentences Resources Image processing was done using the ImageJ software package. ImageJsuggested: (ImageJ, RRID:SCR_003070)Data were processed using the FlowJo software package. FlowJosuggested: (FlowJo, RRID:SCR_008520)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 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.
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