Mucosal Immunization of Cynomolgus Macaques with Adenoviral Vector Vaccine Elicits Neutralizing Nasal and Serum Antibody to Several SARS-CoV-2 Variants

  1. Becca A. Flitter
  2. Colin A. Lester
  3. Sarah N. Tedjakusuma
  4. Emery G. Dora
  5. Nadine Peinovich
  6. Mario Cortese
  7. Clarissa I. Martinez
  8. Clara B. Jegede
  9. Elena D. Neuhaus
  10. Sean N. Tucker

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Abstract

The emergence of SARS-CoV-2 variants continues to be a major obstacle for controlling the global pandemic. Despite the currently authorized SARS-CoV-2 vaccines ability to reduce severe disease and hospitalization, new immunization strategies are needed that enhance mucosal immune responses, inhibit community transmission, and provide protection against emerging variants. We have developed a mucosally delivered, non-replicating recombinant adenovirus vector (rAd5) vaccine, that has proven efficacy in the clinic against other respiratory viruses [1]. Here we evaluated the immunogenicity of three candidate SARS-CoV-2 vaccines in cynomolgus macaques that contained spike (S) and/or nucleocapsid (N) from either the Wuhan or the beta variant to select a candidate for future clinical development. Mucosal immunization with the Wuhan specific S vaccine (ED90) induced significant cross-reactive serum IgG responses against to Wuhan, beta, gamma and delta lineages, and generated substantial serum neutralizing activity. In nasal samples, ED90 immunization induced 1000-fold increases in IgA to all variants of concern tested and had neutralizing activity against Wuhan and delta. While immunization with the beta specific vaccine (ED94) enhanced IgG and IgA responses to homologous beta variant S and RBD, this approach resulted in less cross-reactive responses to other variants in the serum and nasal passages compared to ED90. As ED90 immunization induced the most robust cross-reactive systemic and mucosal antibody responses, this candidate was chosen for future clinical development.

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  1. Version published to 10.1101/2022.02.21.481345v2 on bioRxiv
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    SciScore for 10.1101/2022.02.21.481345: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableAnimals and study design: Twenty cynomolgus macaques were randomly assigned to five groups (n = 4 animals) comprising of two males and two females.
    RandomizationAnimals and study design: Twenty cynomolgus macaques were randomly assigned to five groups (n = 4 animals) comprising of two males and two females.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum IgG and IgA antibody responses against SARS-CoV-2 variants: Serum IgG and IgA to responses to full length S protein and RBD was quantified against Wuhan and alpha, beta and gamma variants, using V-PLEX SARS-CoV-2 panel 7 (Meso Scale Diagnostics, MD)
    IgA
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Vero E6 cells (ATCC, cat# CRL-1586) were plated in 24-well plates at 175,000 cells/well in DMEM + 10% FBS + Gentamicin, until cells reached 80 -100% confluency the following day.
    Vero E6
    suggested: RRID:CVCL_XD71)

    Results from OddPub: Thank you for sharing your data.

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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

    About SciScore

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  3. Version published to 10.1101/2022.02.21.481345v1 on bioRxiv