Circular RNA lipid nanoparticle vaccine against SARS-CoV-2

Area of Science:

• Biotechnology
• Vaccinology
• Immunology

Background:

• Messenger RNA (mRNA) vaccines are widely used for SARS-CoV-2, but circular RNA (circRNA) offers potential advantages like increased stability and reduced immunogenicity.
• Intracellular delivery technologies for circRNA remain underdeveloped, hindering its vaccine applications.

Purpose of the Study:

• To develop an optimized lipid nanoparticle (LNP) platform for efficient intracellular delivery of protein-coding circRNA.
• To evaluate the efficacy of circRNA-based vaccines against SARS-CoV-2 in preclinical models.

Main Methods:

• Utilized a design-of-experiments (DoE) methodology to optimize circRNA LNP formulation parameters.
• Assessed circRNA LNP delivery, transgene expression, immune cell maturation, and vaccine efficacy in vitro and in vivo (mice).
• Compared immune responses elicited by circRNA LNPs versus mRNA LNPs against SARS-CoV-2 antigens.

Main Results:

• Achieved strong and durable transgene expression with the optimized circRNA LNP platform.
• Demonstrated substantial accumulation of circRNA LNPs in draining lymph nodes and potent dendritic cell (DC) maturation post-administration.
• circRNA LNP vaccination induced robust antibody production, enhanced T_h1-biased cellular responses, and significantly higher antigen-specific IgG titers compared to mRNA LNPs.

Conclusions:

• The optimized circRNA LNP platform facilitates effective circRNA delivery to immune cells, leading to enhanced vaccine efficacy.
• circRNA LNPs represent a promising alternative to mRNA LNPs for developing next-generation vaccines against infectious diseases like SARS-CoV-2.