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.

KEYWORDS:

• mRNA vaccine
• adjuvant
• innate immunity
• mRNA delivery
• lipid nanoparticle
• polyplex
• antigen-presenting cell
• lymphoid organ

Disclosure statement

S.U. is a founder of Crafton Biotechnology.

Additional information

Funding

This work was supported by Grants-in-Aid for Scientific Research (A) [21H04962 to S.U.] from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT), Leading Advanced Projects for Medical Innovation [21gm0010008s0101 to S.U.], Research Programme on Emerging and Re-emerging Infectious Diseases [21fk0108620h0001 to S.U.], the Research on Development of New Drugs [23ak0101173 to S.U.] from Japan Agency for Medical Research and Development (AMED).