Capricor Therapeutics has shared early data on the exosome-mediated delivery of COVD-19 vaccines. The preclinical work furthers Capricor’s efforts to show its exosomes are a better delivery vehicle for mRNA than the currently used lipid nanoparticles (LNPs).
LNPs have facilitated early breakthroughs in the use of mRNA. However, Capricor sees opportunities to improve on the safety and expression of mRNA vaccines that use LNPs as delivery vehicles.
Capricor shared preclinical data to support its hypothesis in a preprint paper. The paper describes the creation of exosomes and LNPs loaded with mRNA. At low doses, expression was 25% higher in cells treated with the exosome formulation. The difference was larger still at the high dose, leading the researchers to posit that “LNP administration is inhibitory at high levels of administration.”
The researchers assessed the safety of exosomes and LNPs by giving mice one or the other of the delivery vehicles. After three days, none of the animals in the control or exosome groups had organ abnormalities. In contrast, four-fifths of the mice that received LNPs had abnormal spleen histology.
Further research focused on the use of exosomes in COVID-19 vaccines designed to induce antibody responses against both the spike and nucleocapsid protein. At doses equivalent to 0.25 ug and 4 ug, well below the 100 ug used in Moderna’s COVID-19 vaccine, researchers found antibody responses “were not particularly robust but they were long-lasting.”
A limited antibody response against the nucleocapsid was expected as that element of the vaccine is intended to induce cellular immunity. The researchers saw “a significant increase in the percentages of CD4+ T-cells and CD8+ T-cells,” leading them to conclude that the vaccine achieved its primary goal of priming the cellular arm of the immune system.
Capricor, like some other biotechs including ImmunityBio, sees a need for products that go beyond the spike-focused immunity conferred by existing vaccines. “Spike-only vaccines are susceptible to escape effects whenever an antigenically shifted Spike variant starts to spread in susceptible populations,” researchers from Capricor and its collaborators at Johns Hopkins University School of Medicine wrote in the preprint.