Serological response to extralabel use of parenteral rabies vaccines in 28 mammalian species

Objective: To evaluate immunogenicity, persistence of antibodies, survival after challenge, and anamnestic response following extralabel parenteral rabies vaccination across mammalian species compared with benchmarks from on-label canine vaccination. Methods: Mammals described in published studies of extralabel parenteral rabies vaccination. A structured literature review (1980 to 2025) identified studies reporting serologic or challenge outcomes after extralabel parenteral rabies vaccination. Extracted data included taxonomic family; vaccine type and schedule, timing of serum collection, antibody titers, survival after experimental challenge, and response to booster vaccination. Random-effects meta-analyses were conducted by family and overall. Pooled proportions were compared with the World Organisation for Animal Health benchmark of 88% survival and with canine benchmarks for primary seroconversion (88.1%), antibody levels 6 to 12 months after primary vaccination (72.9%), and booster response (96.8%). Results: 32 articles describing 41 studies met inclusion criteria, representing 2,630 animals from 28 species in 17 families. After primary vaccination, 84.4 ± 4.1% achieved titers ≥ 0.5 IU/mL, with 14 of 16 families noninferior to the canine benchmark. At ≥ 6 months, 63.7 ± 10.6% maintained titers ≥ 0.5 IU/mL. Among 79 vaccinated animals challenged with rabies virus, 89.0 ± 9.8% survived. Booster vaccination produced adequate titers in 89.1 ± 8.0% of 275 animals, with reduced responses in the families Elephantidae and Ursidae. Conclusions: Modern-day rabies vaccines generate strong antibody responses across diverse mammalian families, with nondomestic canids responding similarly to domestic dogs. Clinical Relevance: These findings support recognizing extralabel vaccination as biologically protective and can inform public health and animal management policies.