Unlocking Protective Immunity with Multivalent RNA Vaccines: Insights from a Novel Localizing Nanocarrier Approach


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Our recent study delineated a novel strategy for the delivery of multivalent replicating RNA (repRNA) vaccines via a localizing cationic nanocarrier formulation, LION™, contrasting with the conventional lipid nanoparticles (LNP). We found that LION™ formulation would mitigate systemic inflammatory responses and limit vaccine biodistribution to the site of administration, thus enhancing the safety profile of repRNA vaccines while preserving immunogenic efficacy. Experimental outcomes confirmed that the LION™ platform facilitated localized delivery of repRNA, engendering significant innate immune activation within the injection site and draining lymph nodes devoid of systemic inflammatory responses. Comparative immunological assessments in murine models revealed that LION™-formulated repRNA vaccines elicited robust adaptive immune responses, analogous to those triggered by LNP-based vaccines, albeit without the reactogenicity commonly associated with LNPs. Of note, in a multivalent composition, repRNA delivered by LION but not LNP induced the pulmonary protective response against Enterovirus D68 in mice. These findings advocate for the LION™ system’s utility as a promising nanocarrier for multivalent RNA vaccines, highlighting the potential of this platform for counteracting emerging virus threats.


Taishi Kimura, PhD

Senior Scientist , HDT Bio

Taishi Kimura, a Senior Scientist at HDT Bio, Seattle, specializes in virology, innate immunology, and RNA vaccinology. Through his doctoral training at Osaka University in Japan, postdoctoral training at Scripps Research in La Jolla, and current work at HDT Bio, his work focuses on innate immune responses to viruses and RNA vaccines. Kimura has contributed to various research projects, including his recent publication in Molecular Therapy, uncovering the mechanistic insight into the safety profile of HDT Bio’s RNA vaccine platform.