The Nucleocapsid Protein Of SARS-CoV-2, Combined With ODN-39M, Is A Potential Component For An Intranasal Bivalent Pancorona Vaccine

  1. Yadira Lobaina
  2. Rong Chen
  3. Edith Suzarte
  4. Panchao Ai
  5. Vivian Huerta
  6. Alexis Musacchio
  7. Ricardo Silva
  8. Changyuan Tan
  9. Alejandro Martin
  10. Laura Lazo
  11. Gerardo Guillén
  12. Ke Yang
  13. Yasser Perera
  14. Lisset Hermida

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Abstract

Despite the rapid development of vaccines and their reported efficacy for controlling the COVID-19 waves, two key challenges remain: the scope of the immunity against upcoming variants and zoonosis events, and the induction of mucosal immunity able to clear the virus in the upper respiratory tract for halting the transmission. The present study is aiming at assessing a potential component for a new generation of vaccines so as to overcome such limitations. The recombinant nucleocapsid (N) protein from SARS-CoV-2 Delta variant was combined with a phosphodiester backbone CpG ODN (ODN-39M), forming high molecular weight aggregates. The evaluation of its immunogenicity in Balb/C mice revealed that only administration by intranasal route induced a systemic cross-reactive Cell-Mediated-Immunity (CMI). In turn, this combination was able to induce anti-N IgA in lungs, which along with the specific IgG in sera and CMI in spleen, resulted cross-reactive against the nucleocapsid protein of SARS-CoV-1. Furthermore, the nasal administration of the N+ODN-39M preparation combined with the RBD Delta protein, as inductor of neutralizing Abs, enhanced the local and systemic immune response against RBD with a modulation toward a Th1 pattern. Taken together, these results make the N+ODN-39M preparation a suitable component for a future intranasal pancorona vaccine against Sarbecoviruses. Particularly, the bivalent vaccine formulation N+ODN-39M+RBD could be used as an effective nasal booster in previously vaccinated population.

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    SciScore for 10.1101/2022.06.02.494502: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: All the experimental protocols were approved by Institutional Animal Care and Use Committee.
    Sex as a biological variableImmunization experiments: Adult (6 to 8 weeks old) females Balb/c mice (inbred, H-2d) were housed at Beijing Vital River Laboratory Animal Technology Co
    RandomizationSamples (three or five mice per group) were processed individualized, with the exception of the control groups (Placebos) which were processed as pooled samples of three randomly selected mice.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Assessment of cellular immune response by IFN-γ ELISPOT: IFN-γ ELISPOT assay was performed using a Mouse IFN-γ ELISpot antibody pair (Mabtech, Sweden).
    IFN-γ
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Immunization experiments: Adult (6 to 8 weeks old) females Balb/c mice (inbred, H-2d) were housed at Beijing Vital River Laboratory Animal Technology Co
    Balb/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    Software and Algorithms
    SentencesResources
    Statistical analysis: For statistical analyses the GraphPad Prism version 5.00 statistical software (
    GraphPad
    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2022.06.02.494502v1 on bioRxiv