Durability of next-generation self-replicating RNA vaccine RBI-4000: a phase 1, randomized open label clinical trial

Area of Science:

• Vaccinology
• Immunology
• Molecular Biology

Background:

• mRNA vaccines offer rapid development but may lack durable immunity compared to traditional vaccines.
• Self-replicating RNA (srRNA) platforms show potential for inducing sustained immune responses at lower doses.
• A Phase 1 trial demonstrated the immunogenicity of RBI-4000, a srRNA rabies vaccine, across tested doses.

Purpose of the Study:

• To assess the durability of immune responses elicited by the srRNA rabies vaccine, RBI-4000, up to 8 months post-immunization.
• To compare the long-term immunogenicity of RBI-4000 against a commercial inactivated rabies vaccine (RabAvert).

Main Methods:

• Secondary outcome analysis of a Phase 1 clinical trial (NCT06048770) involving 89 healthy adults.
• Measurement of rabies virus neutralizing antibody titers up to 8 months post-vaccination.
• Statistical modeling, including post-hoc analysis, to compare durability between RBI-4000 and RabAvert.

Main Results:

• Rabies virus neutralizing antibody titers remained above seropositivity benchmarks at 8 months in all RBI-4000 study cohorts.
• Statistical decay modeling indicated that RBI-4000 induced antibody durability comparable to or better than RabAvert.
• The study provides the first head-to-head durability data for an optimized srRNA rabies vaccine.

Conclusions:

• The optimized self-replicating RNA rabies vaccine, RBI-4000, elicits sustained immune responses.
• RBI-4000 demonstrates comparable or improved long-term immunogenicity relative to a traditional inactivated rabies vaccine.
• These findings support the potential of srRNA technology for developing vaccines with durable protective immunity.