Evaluation of the immunobiological properties of an oral briquette rabies vaccine in foxes

Main Article Content

Authors

Y.A. Bulatov

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

R.T. Abitayev

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

A.K. Ussembay

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

Zh.T. Amanova

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

Zh.Zh. Sametova

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

Sh.S. Turyskeldi

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan
Al-Farabi Kazakh National University, Faculty of Biology and Biotechnology, 71 Al-Farabi Avenue, Almaty, 050040, Republic of Kazakhstan

 

Zh.B. Kondibayeva

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

D.M. Mazbayeva

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

A.K. Kurmasheva

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

Zh.K. Koshemetov

 Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan

J.G. Renukaradhya

The Ohio State University, Department of Animal Sciences, Animal Science Building 2029 Fyffe Road, Columbus, 43210, Ohio State, USA

D.S. Toktyrova

Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, 25/1, Gvardeiskiy, Korday District, Zhambyl Region, 080409, Kazakhstan
Al-Farabi Kazakh National University, Faculty of Biology and Biotechnology, 71 Al-Farabi Avenue, Almaty, 050040, Republic of Kazakhstan

Abstract

Rabies remains one of the most dangerous zoonotic infections maintained in natural reservoirs among wild carnivorous animals. Despite the high efficacy of inactivated vaccines in domestic animals, rabies control in wildlife requires the use of oral vaccines capable of providing mass immunization of naturally susceptible species. The aim of the present study was to evaluate the immunogenicity, safety, and protective efficacy of an oral briquetted rabies vaccine tested in naturally susceptible carnivorous animals. Clinically healthy rabies-seronegative foxes were used in the experiment. To assess immunogenicity, animals received a single oral administration of a briquetted vaccine containing a fixed rabies virus strain. Vaccine safety was evaluated using an increased dose (10 baits per animal). The dynamics of the humoral immune response were assessed using the mouse neutralization test and ELISA. Protective efficacy was determined by challenge infection with the CVS test strain. The results demonstrated that the vaccine was readily consumed by the animals and did not cause clinical adverse reactions or deviations from physiological norms. Vaccinated animals developed a pronounced humoral immune response, with mean virus-neutralizing antibody titers exceeding the protective level of 0.5 IU/ml and reaching peak values on day 21 post-immunization. Following challenge infection, all vaccinated animals survived and showed no clinical signs of rabies, whereas control animals developed the paralytic form of the disease with a fatal outcome. Thus, the obtained data demonstrate the high immunogenicity, safety, and protective efficacy of the oral briquetted rabies vaccine and confirm its potential for use in oral immunization programs targeting carnivorous wildlife species and the control of natural rabies foci.

Keywords

rabies, oral vaccination, briquetted vaccine, virus-neutralizing antibodies, wild carnivores

Article Details

References

Dietzschold B., Li J., Faber M., Schnell M. Concepts in the pathogenesis of rabies // Future Virology. – 2008. – Vol. 3. – No 5. – P. 481-490. Crossref

Shiraishi R., Nishimura M., Nakashima R., Enta C., Hirayama N. Neutralizing Antibody Response in Dogs and Cats Inoculated with Commercial Inactivated Rabies Vaccines // Journal of Veterinary Medical Science. – 2014. – Vol. 76. – 4. – P. 605-609. Crossref

Moore S.M., Gilbert A., Vos A., et al. Rabies Virus Antibodies from Oral Vaccination as a Correlate of Protection against Lethal Infection in Wildlife // Tropical Medicine and Infectious Disease. – 2017. – Vol. 2. – No. 3. – P. 31. Crossref

Steck F., Wandeler A., Bichsel P., Capt S., Häfliger U., Schneider L. Oral immunization of foxes against rabies laboratory and field studies // Comparative Immunology, Microbiology and Infectious Diseases. – 1982. – Vol. 5. 1-3. – P. 165-171. Crossref

Wandeler A.I., Capt S., Kappeler A., Hauser R. Oral immunization of wildlife against rabies: concept and first field experiments // Reviews of Infectious Diseases. – 1988. – Vol. 10 – Suppl 4. – P. 649-653. Crossref

WHO. Zero by 30: the global strategic plan to end human deaths from dog-mediated rabies by 2030. – 2018. URL

Zero by 30 the global strategic plan human deaths from dog-mediated rabies by 2030 to end // WOAH – 2018. URL

Brown D., Fooks A.R., Schweiger M. Using Intradermal Rabies Vaccine to Boost Immunity in People with Low Rabies Antibody Levels // Advances in Preventive Medicine. – 2011. – P. 1-5. Crossref

Rosatte R., Donovan D., Allan M., et al. Rabies in Vaccinated Raccoons from Ontario, Canada // Journal of Wildlife Diseases. – 2007. – Vol. 43. 2. – P. 300-301. Crossref

Rosatte R., Donovan D.M., Allan M., et al. Emergency response to raccoon rabies introduction into Ontario // Journal of Wildlife Diseases. – 2001. – Vol. 37(2). – P. 265-279. Crossref

Freuling C.M., Eggerbauer E., Finke S., et al. Efficacy of the oral rabies virus vaccine strain SPBN GASGAS in foxes and raccoon dogs // Vaccine. – 2019. – Vol. 37(33). – P. 4750-4757. Crossref

Sterner R.T., Meltzer M.I., Shwiff S.A., Slate D. Tactics and Economics of Wildlife Oral Rabies Vaccination, Canada and the United States // Emerging Infectious Diseases. – 2009. – Vol. 15(8). – P. 1176-1184. Crossref

Hartinger J., Folz T., Cussler K. Clinical endpoints during rabies vaccine control tests // ALTEX. – 2001. – 18(1):37-40. URL

Müller T., Freuling C.M. Rabies Vaccines for Wildlife // In: Ertl, H (eds) Rabies and Rabies Vaccines Springer, Cham. – 2020. – P. 45-70. Crossref

Overduin, van Dongen, Visser. The Cellular Immune Response to Rabies Vaccination: A Systematic Review // Vaccines. – 2019. – Vol. 7(3):110. Crossref

European Medicines Agency (EMA). Rabies Vaccine (Live, Oral) for Foxes and Raccoon Dogs // Monograph 0746 01/2014, 9th ed. – Ph, E., Ed. – Council of Europe: Strasbourg, France. – 2016.

Bommier E., Chapat L., Guiot A.L., et al. Multivariate analysis of the immune response to different rabies vaccines // Veterinary Immunology and Immunopathology. – 2020. – T. 220:109986. Crossref

Chapat L., Hilaire F., Bouvet J., et al. Multivariate analysis of the immune response to a vaccine as an alternative to the repetition of animal challenge studies for vaccines with demonstrated efficacy // Veterinary Immunology and Immunopathology. – 2017. – Vol. 189. – P. 58-65. Crossref

Vogt R., Schulte P.A. Evaluation of immune responses // IARC scientific publications. – 2011. – Vol. 163. – P. 215-239. URL

Wang Z.W., Sarmento L., Wang Y., et al. Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System // Journal of Virology. – 2005. – Vol. 79(19). – P. 12554-12565. Crossref

Verena te Kamp, Freuling C.M., Vos A., et al. Responsiveness of various reservoir species to oral rabies vaccination correlates with differences in vaccine uptake of mucosa associated lymphoid tissues // SCI Rep. – 2020 – Vol. 10(1). Crossref

Ghislat G., Lawrence T. Autophagy in dendritic cells // Cellular & Molecular Immunology. – 2018. – Vol. 15(11). – P. 944-952. Crossref

Roy A., D. Craig Hooper. Lethal Silver-Haired Bat Rabies Virus Infection Can Be Prevented by Opening the Blood-Brain Barrier // J Virol. – 2007. – Vol. 81(15). – P. 7993-7998. Crossref

Zhang S., Hao M., Feng N., et al. Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice // Viruses. – 2019. – T. 11. – Vol. 10. 919. Crossref

Lebrun A., Garcia S., Li J., Kean R., Hooper D. Protection Against CNS-Targeted Rabies Virus Infection is Dependent upon Type-1 Immune Mechanisms Induced by Live-Attenuated Rabies Vaccines // Tropical Medicine and Infectious Disease. – 2017. – T. 2. – Vol. 3:22. Crossref

Gnanadurai C.W., Yang Y., Huang Y., et al. Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs // Rupprecht CE, ed. PLOS Neglected Tropical Diseases. – 2015. – T. 9. – Vol. 8. Crossref

Bulatov Y., Koshemetov Z., Amanova Z., Abitayev R., Ussembay A., Sametova Z., Kondybaeva Z., Kurmasheva A., Mazbayeva D., Turyskeldy S., Toktyrova D. SAFETY ASSESSMENT OF AN ORAL RABIES VACCINE BAIT FOR WILD CARNIVORES IN A SERONEGATIVE DOG MODEL // Eurasian Journal of Applied Biotechnology. – 2025. – Vol. 3. – P. 93-101. Crossref

Kiflu A.B. The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms // Viruses. – 2024. – T. 16. – Vol. 11.1774. Crossref