Two mRNA Platforms for Canine Rabies Vaccines: Advances, Limitations, and Field Application Prospects.

Canine rabies control in rural China faces logistical barriers such as multi-dose schedules, cold-chain requirements, and the recapture of free-roaming dogs, which impede progress toward 70% vaccination coverage. Although inactivated vaccines remain the cornerstone of rabies control, mRNA platforms offer both manufacturing and immunological advantages. This review compares non-replicating mRNA (nr-mRNA) and self-amplifying mRNA (saRNA) platforms. It also examines oral and vectored vaccines as comparators for free-roaming dogs beyond the reach of injectable products. LVRNA001 and ABO1005 are nr-mRNA candidates that provide complete protection in canine challenge models using two-dose regimens; neutralizing antibody geometric mean titers (GMTs) exceed the World Health Organization (WHO) 0.5 IU/mL threshold through day 125, with the LVRNA001 50-μg group reaching approximately 100 IU/mL versus approximately 16 IU/mL for the inactivated vaccine (P<0.05). Both elicited Th1-biased cellular and cross-neutralizing antibody responses; lyophilized ABO1005 was stable at 2-8 °C for 12 months. For saRNA, single-dose protection has been shown only in mice and no canine data exist; dose extrapolation and excessive innate immune activation remain unresolved. Licensure requires compliance with China's 2026 draft guideline for animal mRNA products. Evidence derives from human candidates in beagles; prospects are most immediate for owned or accessible dogs; translation remains contingent on target-animal safety data, delivery innovation, regulatory approval, and operational feasibility.