Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Exosome based multivalent vaccine: achieving potent immunization, broadened reactivity, and strong T cell responses with nanograms of proteins

View ORCID ProfileMafalda Cacciottolo, View ORCID ProfileJustin B Nice, Yujia Li, Michael J. LeClaire, Ryan Twaddle, Ciana Mora, Stephanie Y. Adachi, Esther R. Chin, Meredith Young, Jenna Angeles, Kristi Elliott, Minghao Sun
doi: https://doi.org/10.1101/2023.01.10.523356
Mafalda Cacciottolo
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mafalda Cacciottolo
Justin B Nice
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Justin B Nice
Yujia Li
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael J. LeClaire
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryan Twaddle
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ciana Mora
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephanie Y. Adachi
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Esther R. Chin
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Meredith Young
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jenna Angeles
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristi Elliott
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minghao Sun
Capricor Therapeutics, Inc., 10865 Road to the Cure, San Diego, CA, 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: msun@capricor.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Current approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first vaccines were developed rapidly using spike mRNA delivered by lipid nanoparticles but required ultra-low storage and have had limited immunity against variations in spike. Subsequently, protein-based vaccines were developed which offer broader immunity but require significant time for development and use of an adjuvant to boost immune response. Here, exosomes were used to deliver a bi-valent protein-based vaccine, in which two independent viral proteins were used. Exosomes were engineered to express either SARS-CoV-2 Delta spike (Stealth X-Spike, STX-S) or the more conserved nucleocapsid (Stealth X-Nucleocapsid, STX-N) protein on the surface. When administered as single product (STX-S or STX-N) or in combination (STX-S+N), both STX-S and STX-N induced a strong immunization with the production of a potent humoral and cellular immune response. Interestingly, these results were obtained with administration of only nanograms of protein and without adjuvant. In two independent animal models (mouse and rabbit), administration of nanograms of the STX-S+N vaccine resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other variants of spike and strong T-cell responses. Importantly, no competition in immune response was observed, allowing for delivery of nucleocapsid with spike to offer improved SARS-CoV-2 immunity. These data show that the StealthXTM exosome platform has an enormous potential to revolutionize vaccinology by combining the advantages of mRNA and recombinant protein vaccines into a superior, rapidly generated, low dose vaccine resulting in potent, broader immunity.

Competing Interest Statement

The authors are employees of Capricor Therapeutics.

Footnotes

  • The manuscript was edited for typos and misspelling errors. No changes were made to the results or conclusions of the paper.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 19, 2023.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Exosome based multivalent vaccine: achieving potent immunization, broadened reactivity, and strong T cell responses with nanograms of proteins
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Exosome based multivalent vaccine: achieving potent immunization, broadened reactivity, and strong T cell responses with nanograms of proteins
Mafalda Cacciottolo, Justin B Nice, Yujia Li, Michael J. LeClaire, Ryan Twaddle, Ciana Mora, Stephanie Y. Adachi, Esther R. Chin, Meredith Young, Jenna Angeles, Kristi Elliott, Minghao Sun
bioRxiv 2023.01.10.523356; doi: https://doi.org/10.1101/2023.01.10.523356
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Exosome based multivalent vaccine: achieving potent immunization, broadened reactivity, and strong T cell responses with nanograms of proteins
Mafalda Cacciottolo, Justin B Nice, Yujia Li, Michael J. LeClaire, Ryan Twaddle, Ciana Mora, Stephanie Y. Adachi, Esther R. Chin, Meredith Young, Jenna Angeles, Kristi Elliott, Minghao Sun
bioRxiv 2023.01.10.523356; doi: https://doi.org/10.1101/2023.01.10.523356

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4662)
  • Biochemistry (10319)
  • Bioengineering (7647)
  • Bioinformatics (26263)
  • Biophysics (13485)
  • Cancer Biology (10653)
  • Cell Biology (15371)
  • Clinical Trials (138)
  • Developmental Biology (8471)
  • Ecology (12783)
  • Epidemiology (2067)
  • Evolutionary Biology (16803)
  • Genetics (11374)
  • Genomics (15436)
  • Immunology (10585)
  • Microbiology (25096)
  • Molecular Biology (10175)
  • Neuroscience (54260)
  • Paleontology (399)
  • Pathology (1663)
  • Pharmacology and Toxicology (2884)
  • Physiology (4329)
  • Plant Biology (9216)
  • Scientific Communication and Education (1583)
  • Synthetic Biology (2545)
  • Systems Biology (6764)
  • Zoology (1459)