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Oral Rabies Vaccines for Wildlife.

Rabies is a nearly 100% fatal zoonotic disease causing ~59,000 human deaths annually, maintained by wildlife reservoirs where oral vaccination is the only scalable control strategy. Current oral vaccines, based on live-attenuated or recombinant viruses, show variable immunogenicity across species and environments.

Saponin adjuvants present a scientific background for immunizations against rabies (2 vaccines) and have been studied for oral or sublingual administration.

Saponin-based adjuvants elicit predominantly Th1 immune response inducing significant production of neutralizing antibody titers, above 0.5 UI/mL, particularly following a challenge event, demonstrated in cats, dogs, mice, and allowing high survival rate when injected. When administered orally, saponin adjuvants have also been able to induce the production of IgG1, IgG2 and IgA titers, enabling higher survival rate as well, across several animal species.

Additionally, CD4⁺ Th1 and CD8⁺ cellular responses through saponin adjuvants may therefore significantly improve the efficacy and immunological memory of oral rabies vaccines.

Saponin adjuvants are able enhance mucosal immunizations and are suitable for oral administration.

The integration of saponin adjuvant into oral rabies vaccines represents a scientifically grounded and relevant direction for the immunization of wildlife.

References
1. Cao, H. et al., 2025. A QS21+ CpG-Adjuvanted Rabies Virus G Subunit Vaccine Elicits Superior Humoral and Moderate Cellular Immunity. Vaccines, 13(8), p. 887.
2. Fontana, D. S. et al., 2020. Rabies VLPs adjuvanted with saponin-based liposomes induce enhanced immunogenicity mediated by neutralizing antibodies in cattle, dogs and cats. Journal of Virological Methods, Volume 286, pp. 1-6.
3. Mansfield, K. L. et al., 2016. Rabies pre-exposure prophylaxis elicits long-lasting immunity inhumans. Vaccine.
4. Wang, C. et al., 2024. A broadly applicable protein-polymer adjuvant system for antiviral vaccines. EMBO Molecular Medecine.

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