A rapidly adaptable biomaterial vaccine for SARS-CoV-2

  1. Fernanda Langellotto
  2. Benjamin T. Seiler
  3. Jingyou Yu
  4. Mark J. Cartwright
  5. Des White
  6. Chyenne Yeager
  7. Michael Super
  8. Edward J. Doherty
  9. Dan H. Barouch
  10. David J. Mooney

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Abstract

The global COVID-19 pandemic motivates accelerated research to develop safe and efficacious vaccines. To address this need, we leveraged a biomaterial vaccine technology that consists of mesoporous silica rods (MSRs) that provide a sustained release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and adjuvants to concentrate and mature antigen-presenting cells at the vaccine site. Here we explored the humoral responses resulting from the use of monophosphoryl lipid A (MPLA) as the adjuvant and SARS-CoV-2 spike proteins S1, S2, the nucleocapsid (N) protein, and receptor binding domain (RBD) as the target antigens. The dose of antigen and impact of pre-manufacturing of vaccines as versus loading antigen just-in-time was explored in these studies. Single shot MSR vaccines induced rapid and robust antibody titers to the presented antigens, even without the use of a boost, and sera from vaccinated animals demonstrated neutralizing activity against a SARS-CoV-2 pseudovirus. Overall, these results suggest the MSR vaccine system may provide potent protective immunity when utilized to present SARS-CoV-2 antigens.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.07.192203: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Mice are maintained under specific pathogen-free conditions at Harvard University, and all experiments are conducted in accordance with animal use guidelines and protocols approved by the Harvard University Animal Care and Use Committee (IACUC).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAnimals and vaccination: Eight-week-old BALB/c female mice (n=10 per group) were vaccinated subcutaneously in the flank using an 18G needle.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Briefly, the packaging construct psPAX2 (AIDS Resource and Reagent Program), luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene, USA), and spike protein expressing pcDNA3.1-SARS CoV-2 SΔCT were co-transfected into HEK293T cells with calcium phosphate.
    HEK293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    To determine the neutralization activity of the antisera from vaccinated animals, HEK293T-hACE2 cells were seeded in 96-well tissue culture plates at a density of 1.75 x 104 cells/well overnight.
    HEK293T-hACE2
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Animals and vaccination: Eight-week-old BALB/c female mice (n=10 per group) were vaccinated subcutaneously in the flank using an 18G needle.
    BALB/c
    suggested: None
    Software and Algorithms
    SentencesResources
    Standard curve OD readouts on each plate were used to create a 4PL-sigmoidal curve to interpolate sample data, which was analyzed, processed, and presented using GraphPad Prism 8 (version 8.1.2).
    GraphPad Prism
    suggested: (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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.07.07.192203v1 on bioRxiv