Multiple nucleic acid vaccines are currently in clinical trials for COVID-19 yet the mechanisms by which nucleic acid vaccines elicit immune responses remains largely unknown. For example, how are mRNA vaccines processed in lymph nodes after injection? What can be done to improve antibody responses? Is there a rational approach to design a single shot vaccine - one that does not require a prime + boost sequence? How do various arms of the immune system respond to foreign mRNA or DNA?
Here we describe, COATSOME, a novel lipid nanoparticle system for delivery of mRNA vaccines that improves antigen expression in lymph nodes macrophages and induces strong T cell responses. Previously we have published data showing COATSOME lipids having very low in-vivo toxicity due to their biodegradable nature and high levels of gene transfection activity. We studied the fate of COATSOME nanoparticles in mice after SC injection and their trafficking to lymph nodes and the biology of the immune response. Certain classes of COATSOME lipids were more potent at inducing protective immunity in mice to pathogen challenge. Through analysis of the biomarker profiles associated with different lipids we begin to understand the nuances of antigen processing with nucleic acid vectors. These initial findings support strategies for rational design of a delivery platform for nucleic vaccine therapeutics. OUR HOPE is that future emerging infections outbreaks can be rapidly responded with by combining speed of mRNA manufacturing with an off-the shelf delivery agent such as COATSOME.
Upon completion participant will be able to understand how ionizable lipids function for cellular delivery of mRNA
Upon completion participant will appreciate the challenge of developing mRNA vaccines
Upon completion participant will be able to explain how the innate immune system detects foreign nucleic acids
Upon completion participants will be able to enumerate the top 3 requirements for successful vaccine products