Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers.

ABSTRACT: Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed in the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions and demonstrate immunogenicity and safety in preclinical and clinical development. Optimized srRNA vaccines generate protective immunity (according to the WHO defined thresholds) at doses up to 1,000,000-fold lower than mRNA in female mouse models of influenza and rabies. Clinically, safety and immunogenicity of RBI-4000, an srRNA vector encoding the rabies glycoprotein, was evaluated in a Phase I study (NCT06048770). RBI-4000 was able to elicit de novo protective immunity in the majority of h

SUBMITTER: Maine CJ 

PROVIDER: S-EPMC11707033 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature