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.