A Thermostable Oral SARS-CoV-2 Vaccine Induces Mucosal and Protective Immunity
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Abstract
An ideal protective vaccine against SARS-CoV-2 should not only be effective in preventing disease, but also in preventing virus transmission. It should also be well accepted by the population and have a simple logistic chain. To fulfill these criteria, we developed a thermostable, orally administered vaccine that can induce a robust mucosal neutralizing immune response. We used our platform based on retrovirus-derived enveloped virus-like particles (eVLPs) harnessed with variable surface proteins (VSPs) from the intestinal parasite Giardia lamblia , affording them resistance to degradation and the triggering of robust mucosal cellular and antibody immune responses after oral administration. We made eVLPs expressing various forms of the SARS-CoV-2 Spike protein (S), with or without membrane protein (M) expression. We found that prime-boost administration of VSP-decorated eVLPs expressing a pre-fusion stabilized form of S and M triggers robust mucosal responses against SARS-CoV-2 in mice and hamsters, which translate into complete protection from a viral challenge. Moreover, they dramatically boosted the IgA mucosal response of intramuscularly injected vaccines. We conclude that our thermostable orally administered eVLP vaccine could be a valuable addition to the current arsenal against SARS-CoV-2, in a stand-alone prime-boost vaccination strategy or as a boost for existing vaccines.
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SciScore for 10.1101/2021.09.09.459634: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: The number of animals for each experiment and all procedures followed the protocols approved by the Institutional Committee for Care and Use of Experimental Animals. Sex as a biological variable Six week- or four month-old male and female BALB/c mice were used for initial experiments, 6-month-old female and male Golden Syrian hamsters were used in the immunization studies, and 1-month-old female and male SPF Golden Syrian hamsters were used in the challenge experiments. Randomization Experimental animals: For immunization and challenge, the group sizes were chosen based on previous experience and littermates of the same sex were randomly assigned. Blinding not detected. Power Analysis not … SciScore for 10.1101/2021.09.09.459634: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: The number of animals for each experiment and all procedures followed the protocols approved by the Institutional Committee for Care and Use of Experimental Animals. Sex as a biological variable Six week- or four month-old male and female BALB/c mice were used for initial experiments, 6-month-old female and male Golden Syrian hamsters were used in the immunization studies, and 1-month-old female and male SPF Golden Syrian hamsters were used in the challenge experiments. Randomization Experimental animals: For immunization and challenge, the group sizes were chosen based on previous experience and littermates of the same sex were randomly assigned. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Enzyme-linked immunosorbent assay (ELISA) tests: The levels of IgG and IgA antibodies against spike protein were determined by ELISA by sensitizing the plate with homogenates of killed whole virus produced in vitro. IgA antibodies against spike proteinsuggested: NoneThe following secondary antibodies were used: Mouse anti-Hamster IgG Cocktail, Clone: G94-56, G70-204 (BD Biosciences, Cat. # 554009); Mouse anti-Hamster IgM, Clone: G188-9, (BD Biosciences Cat. # 554035); Hamster Immunoglobulin A (IgA) ELISA Kit (MyBiosources Cat. # MBS029668); Mouse monoclonal (H6) anti-SARS-CoV-2 spike glycoprotein (Abcam Cat. # ab273169). anti-Hamster IgGsuggested: Noneanti-Hamster IgMsuggested: (BD Biosciences Cat# 554035, RRID:AB_395220)anti-SARS-CoV-2 spike glycoproteinsuggested: (Abcam Cat# ab275759, RRID:AB_2892127)Experimental Models: Cell Lines Sentences Resources Viruses: SARS-CoV-2 isolates were propagated in Vero E6 cells in Opti-MEM I (Invitrogen, Cat. # 51985091) containing 0.3% bovine serum albumin (BSA) and 1 μg of L-1-tosylamide-2-phenylethyl chloromethyl ketone-treated trypsin per mL at 37 °C. Vero E6suggested: NoneVLP generation, production, purification, and validation: VLPs were produced by transient transfection of either HEK293 cells or HEK293-1267 cells, with pGag, pS and its variants, and pM plasmid DNA, using PEI as transfection reagent. HEK293suggested: NoneHEK293-1267suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Six week- or four month-old male and female BALB/c mice were used for initial experiments, 6-month-old female and male Golden Syrian hamsters were used in the immunization studies, and 1-month-old female and male SPF Golden Syrian hamsters were used in the challenge experiments. BALB/csuggested: NoneRecombinant DNA Sentences Resources VLP generation, production, purification, and validation: VLPs were produced by transient transfection of either HEK293 cells or HEK293-1267 cells, with pGag, pS and its variants, and pM plasmid DNA, using PEI as transfection reagent. pMsuggested: RRID:Addgene_64179)Software and Algorithms Sentences Resources Statistical analyses: Prism (GraphPad Software) was used to perform one-way or two-way ANOVA on datasets with Tukey’s multiple comparisons test or the Bonferroni post-test, respectively. Prismsuggested: (PRISM, RRID:SCR_005375)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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