Nanograms of SARS-CoV-2 spike protein delivered by exosomes induce potent neutralization of both delta and omicron variants

  1. Mafalda Cacciottolo
  2. Yujia Li
  3. Justin B. Nice
  4. Michael J. LeClaire
  5. Ryan Twaddle
  6. Ciana L. Mora
  7. Stephanie Y. Adachi
  8. Meredith Young
  9. Jenna Angeles
  10. Kristi Elliott
  11. Minghao Sun

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Abstract

Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricor’s StealthX TM platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection. The STX-S vaccine induced a strong immunization with the production of a potent humoral immune response as demonstrated by high levels of neutralizing antibody not only against the delta SARS-CoV-2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. Additionally, both CD4 + and CD8 + T cell responses were increased significantly after treatment. Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. This is a significantly lower dose than traditional recombinant protein vaccines with no adjuvant required, which makes the StealthX TM exosome platform ideal for the development of multivalent vaccines with a better safety profile. Importantly, our exosome platform allows novel proteins, or variants in the case of SARS-CoV-2, to be engineered onto the surface of exosomes in a matter of weeks, comparable with mRNA vaccine technology, but without the cold storage requirements necessary for mRNA vaccines. The ability to utilize exosomes for cellular delivery of proteins, as demonstrated by STX-S, has enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation at an extremely low dose resulting in a potent, broad antibody response.

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  1. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/8436586.

    Does the introduction explain the objective of the research presented in the preprint? Yes
    Are the methods well-suited for this research? Highly appropriate
    Are the conclusions supported by the data? Somewhat supported
    Are the data presentations, including visualizations, well-suited to represent the data? Somewhat appropriate and clear
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Somewhat clearly
    Is the preprint likely to advance academic knowledge? Somewhat likely
    Would it benefit from language editing? No
    Would you recommend this preprint to others? Yes, but it needs to be improved
    Is it ready for attention from an editor, publisher or broader audience? Yes, after minor changes
    Competing interests

    The author declares that they have no competing interests.

  2. Version published to 10.1371/journal.pone.0290046
  3. Version published to 10.1101/2023.03.20.533560v1 on bioRxiv