mRNA vaccine designs for optimal adjuvanticity and delivery

Abstract

Adjuvanticity and delivery are crucial facets of mRNA vaccine design. In modern mRNA vaccines, adjuvant functions are integrated into mRNA vaccine nanoparticles, allowing the co-delivery of antigen mRNA and adjuvants in a unified, all-in-one formulation. In this formulation, many mRNA vaccines utilize the immunostimulating properties of mRNA and vaccine carrier components, including lipids and polymers, as adjuvants. However, careful design is necessary, as excessive adjuvanticity and activation of improper innate immune signalling can conversely hinder vaccination efficacy and trigger adverse effects. mRNA vaccines also require delivery systems to achieve antigen expression in antigen-presenting cells (APCs) within lymphoid organs. Some vaccines directly target APCs in the lymphoid organs, while others rely on APCs migration to the draining lymph nodes after taking up mRNA vaccines. This review explores the current mechanistic understanding of these processes and the ongoing efforts to improve vaccine safety and efficacy based on this understanding.

mRNA Technology and Mucosal Immunization

“…Second, the reactogenicity of mRNA vaccines—deemed acceptable for intramuscular delivery—may compromise their safety in mucosae due to the exquisite sensitivity of these sites to inflammatory stimuli [ 24 ]. A proper combination of non-stimulatory ionizable lipids combined with select Toll-like receptor (TLR) agonists or stimulator of interferon genes protein (STING) agonists could be effective in delivering mRNA into epithelia and immunocompetent mucosal cells [ 25 ]. In humans, the second dose of COVID-19 mRNA vaccines enhances humoral and cellular immunity but also induces more severe reactogenicity than the first dose [ 26 ].…”