Abstract
Expression-dependent, Spike-only vaccines have been developed, deployed, and shown to be effective in the fight against SARS-CoV-2. However, additional approaches to vaccine development may be needed to meet existing and future challenges posed by emerging Spike variant strains, as well as a likely need for different antigen-delivery systems that are safe and effective for regular, periodic re-administration. We report here the development of mRNA-loaded exosomes, demonstrate that they can mediate the functional expression of heterologous proteins in vitro and in vivo, and have fewer adverse effects than comparable doses of lipid nanoparticles. Furthermore, we applied this approach to the development of an exosome-based, multiplexed mRNA vaccine that drives expression of immunogenic SARS-CoV-2 Nucleocapsid and Spike proteins. This vaccine elicited long-lasting cellular and humoral responses to Nucleocapsid and to Spike, demonstrating that exosome-based mRNA formulations represent a previously unexplored platform in the fight against COVID-19 and other infectious diseases.
Competing Interest Statement
S.J.G is a paid consultant for Capricor, holds equity in Capricor, and is co-inventor of intellectual property licensed by Capricor. S.J.T. is co-inventor of intellectual property licensed by Capricor. C.G. is co-inventor of intellectual property licensed by Capricor. A.S., K.S, J.N., S.S., C.L., and N.A. are employees of Capricor.
Footnotes
The revised version of this paper contains additional data that (1) compares the effects of injecting exosomes of LNPs into mice, (2) compares the relative efficacy of mRNA-loaded exosomes and LNPs at inducing expression of mRNA-encoded Antares2 activity, and (3) demonstrates real-time bioluminescent light emission from mice injected previously exosomes containing Antares2-encoding mRNA.
