Replicate Bioscience, a clinical-stage company pioneering self-replicating RNA (srRNA) technology, announced the publication of long-term immunogenicity data from the Phase I trial of its rabies vaccine candidate, RBI-4000, in Communications Medicine, a Nature portfolio journal.
The article, “Durability of next-generation self-replicating RNA vaccine RBI-4000: a Phase 1, randomized open label clinical trial,” highlights the robust and durable immune responses elicited by RBI-4000, demonstrating potential advantages over traditional inactivated rabies vaccines.
Key Phase I Findings
- Durable Immunity: Two doses of RBI-4000 at 1 or 10 μg elicited 100% detectable rabies virus neutralizing antibodies (RVNA) at 6 months, with 61% and 88% achieving WHO-defined seroprotection, compared to 58% with the commercial inactivated vaccine.
- Single-Dose Feasibility: A single 10 μg administration induced sustained protective immunity.
- Superior Antibody Durability: Post-hoc analyses showed antibody half-lives at least six times longer than the commercial comparator.
- Safety: RBI-4000 was well tolerated at all doses, with no dose-limiting adverse events, serious adverse events, or treatment-related discontinuations.
Parinaz Aliahmad, Ph.D., Head of R&D, Replicate Bioscience:
"These results position our srRNA platform as a promising alternative to traditional vaccine technologies. RBI-4000 achieves protective immunity at low doses, with potential for longer-lasting responses and simplified dosing."
About the Phase I Trial
- Design: Randomized, open-label, Phase I study (NCT06048770)
- Participants: 89 healthy adults, ages 18–45
- Regimens: Prime-boost at 0.1, 1, and 10 μg; single-dose 10 μg cohort
- Comparator: RabAvert®, an approved inactivated rabies vaccine
- Duration: Follow-up through 8 months
All dose levels of RBI-4000 induced de novo protective immune responses. Even the lowest 0.1 μg dose achieved the WHO-established threshold for RVNA responses.
About Rabies
Rabies is endemic in over 150 countries and causes an estimated 59,000 deaths annually, with a nearly 100% mortality rate if untreated. Current vaccines require 3–5 doses and are limited by complex manufacturing, supply shortages, and accessibility challenges. The World Health Organization includes rabies in its 2021–2030 Roadmap for neglected tropical diseases, and the FDA recognizes rabies under the Tropical Disease Priority Review Voucher Program.
About Replicate Bioscience
Replicate Bioscience develops next-generation RNA therapeutics using proprietary srRNA technology to improve bioactivity, immune response potency, and therapeutic index. RBI-4000 demonstrates protective immunity at lower doses than any previously reported RNA-based vaccine. The company is advancing a broad pipeline of srRNA vaccines and therapeutics across infectious disease, immunology, and immuno-oncology.
