Intranasal administration of a VLP-based vaccine against COVID-19 induces neutralizing antibodies against SARS-CoV-2 and Variants of Concerns
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Abstract
Background
The highly contagious SARS-CoV-2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS-CoV-2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of COVID-19 vaccines.
Methods
In the current study, we tested in murine model the immunogenicity of a conventional vaccine platform based on virus-like particles (VLPs) displaying RBD of SARS-CoV-2 for intranasal vaccination. The candidate vaccine, CuMV TT -RBD, has been immunologically optimized to incorporate tetanus-toxin and is self-adjuvanted with TLR7/8 ligands.
Results
CuMV TT -RBD elicited strong RBD- and spike- specific systemic IgG and IgA antibody responses of high avidity. Local immune responses were assessed and results demonstrate strong mucosal antibody and plasma cell production in lung tissue. The induced systemic antibodies could efficiently recognize and neutralize different Variants of Concerns of mutated SARS-CoV-2 RBDs.
Conclusion
In summary, intranasal vaccination with CuMV TT -RBD shows high immunogenicity and induces protective systemic and local specific antibody response against SARS-CoV-2 and its variants.
One sentence summary
Evaluation of an intransal administrated conventional VLP-based vaccine against COVID-19 in a murine model.
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SciScore for 10.1101/2021.09.10.459749: (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 4.1 Mice: All in vivo experiments were performed using (8-12 weeks old) wild-type (wt) female BALB/cOlaHsd mice purchased from Harlan. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources SARS-CoV-2 strains were propagated in VERO E6 cells (ATCC—CRL 1586) in T175 Flasks using Dulbecco’s Modified Eagle’s - high glucose medium (DMEM) (Euroclone, Pero, Italy) supplemented with 2mM L-glutamine (Lonza, Milano, Italy), 100 units/mL penicillin-streptomycin (Lonza, Milano, Italy and 2% fetal bovine serum (FBS) (Euroclo, Pero, Italy). VERO …SciScore for 10.1101/2021.09.10.459749: (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 4.1 Mice: All in vivo experiments were performed using (8-12 weeks old) wild-type (wt) female BALB/cOlaHsd mice purchased from Harlan. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources SARS-CoV-2 strains were propagated in VERO E6 cells (ATCC—CRL 1586) in T175 Flasks using Dulbecco’s Modified Eagle’s - high glucose medium (DMEM) (Euroclone, Pero, Italy) supplemented with 2mM L-glutamine (Lonza, Milano, Italy), 100 units/mL penicillin-streptomycin (Lonza, Milano, Italy and 2% fetal bovine serum (FBS) (Euroclo, Pero, Italy). VERO E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources 4.1 Mice: All in vivo experiments were performed using (8-12 weeks old) wild-type (wt) female BALB/cOlaHsd mice purchased from Harlan. BALB/cOlaHsdsuggested: RRID:MGI:5653315)Recombinant DNA Sentences Resources The amino acid (a.a.) sequence of each RBD was inserted into a pTWIST-CMV-BetaGlobin-WPRE-Neo vector (Twist Bioscience, San Fransico, CA, USA) pTWIST-CMV-BetaGlobin-WPRE-Neosuggested: NoneSoftware and Algorithms Sentences Resources 4.18 Statistical analysis: Data were analyzed and presented as (mean ± SEM) using Student’s t-test or one-way ANOVA as mentioned in the figure legend, with GraphPad PRISM 9. 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 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.
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