Trial reportNature communications2025
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.
Trial report in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06048770 (A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of RBI-4000 in Healthy Volunteers), which is not on this map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of RBI-4000 in Healthy Volunteers
Who cites it
34 citing papers in PubMed.
- Safety and immunogenicity of a single-dose adenovirus-vectored rabies vaccine over 1 year in adults and children in Tanzania: interim data from an ongoing, partly randomised, controlled, phase 1b/2 trial.The Lancet. Infectious diseases · 2026Trial
- Self-amplifying RNA (saRNA) and circular RNA (circRNA) vaccines: Progress, evidence gaps, and translational pathways for durable and scalable immunization.Human vaccines & immunotherapeutics · 2026Review
- Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity.bioRxiv : the preprint server for biology · 2026Article
- Sindbis virus self-amplifying replicon is compatible with modified nucleotides mediating expression and vaccine responsesMolecular therapy. Advances · 2026Article
- A low-dose self-amplifying mRNA vaccine encoding HPV16 E6/E7 induces potent T-cell immunity and antitumor protection in mice.Cancer immunology, immunotherapy : CII · 2026Article
- Enhanced efficacy of a next-generation EEEV self-replicating RNA platform for combination cancer immunotherapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Towards controllable self-amplifying RNA.Nature biomedical engineering · 2026Article
- Deciphering theVaccines · 2026Article
- Pharmaceutical design of mRNA vaccines for endemic infectious diseases: integrating antigen discovery with platform engineering.Clinical and experimental vaccine research · 2026Review
- Article
- Single intramuscular injection of self-amplifying RNA ofScience (New York, N.Y.) · 2026Article
- Opportunities and Challenges of mRNA and VLP Technologies for Pan-Flavivirus Vaccine Development: Focus on Conserved Quaternary Epitope Conformations.International journal of molecular sciences · 2026Review
- Circular RNA therapeutics: a new class of long-acting RNA medicines for oncology, immunology, and rare diseases.Frontiers in immunology · 2026Review
- COVID-19 mRNA vaccines: a prospective outlook from technological innovation to clinical practice.Frontiers in immunology · 2026Review
- A Self-Amplifying RNA Lipid Nanoparticle (saRNA-LNP) Vaccine Provides Effective Protection Against Porcine Epidemic Diarrhea.Transboundary and emerging diseases · 2026Article
- Working towards a single-dose vaccine for rabies post-exposure prophylaxis.Future virology · 2026Article
- Signatures of Trained Immunity Following mRNA Vaccination: Differences Between mRNA-1273 and BNT162b2.Journal of clinical immunology · 2025Article
- Lipid nanoparticle-based mRNA platforms for mucosal HIV vaccines: formulation advances, immune mechanisms, and translational pathways.Archives of microbiology · 2025Review
- Engineering Anti-Tumor Immunity: An Immunological Framework for mRNA Cancer Vaccines.Vaccines · 2025Review
- Divergent Delivery and Expression Kinetics of Lipid and Polymeric Nanoparticles across mRNA Modalities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors.
Funding
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 healthy participants when administered at a dose of 0.1, 1, or 10 microgram (71%, 94%, 100%, respectively) in a prime-boost schedule. Similarly, we observe immunity above the WHO benchmark of protection following a single administration in most participants at both 1 and 10 microgram doses. There are no serious adverse events reported across all cohorts. These data establish the high therapeutic index of optimized srRNA vectors, demonstrating feasibility of both low dose and single dose approaches for vaccine applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.