Protective immune response of oral rabies vaccine in stray dogs, corsacs and steppe wolves after a single immunization

Abstract

In this study the safety and protective immunity of an oral rabies vaccine, based on the live, modified rabies virus strain VRC-RZ2, was examined in stray dogs (Canis Sp.), corsacs (Vulpes corsac) and steppe wolves (Canis lupus campestris). In the safety group (dogs, n=6; corsacs, n=3; wolves, n=3) which was vaccinated with a 10-times field dose/animal, no animals showed any signs of disease or changes in behavior or appetite during the period of clinical observation, similar to the animals in the negative control group. Saliva samples taken from animals prior and post (5 and 10 days) vaccination failed to demonstrate rabies virus antigen. Observations of immunogenicity in vaccinated carnivores (dogs, corsacs and wolves) during a 180 day period showed the titers of virus neutralizing antibodies (VNA) in the blood sera of vaccinated dogs to be within 0.59-1.37 IU/mL. On 14 days post vaccination (dpv), all the wild carnivores had detectable levels of neutralizing antibodies, with mean titers ranging from 0.50 ± 0.07 IU/mL (for wolves) to 0.59 ± 0.10 IU/mL (for corsacs). Weeks after vaccination, all the vaccinated wolves and corsacs had higher levels of neutralizing antibodies: 0.70 ± 0.10 - 0.71 ± 0.08 IU/mL at 30 dpv, 1.06 ± 0.08 - 1.28 ± 0.21 IU/mL at 60 dpv and 0.41 ± 0.09 - 047 ± 0.06 at 180 dpv. The highest level of VNA (˃1.0 IU/ml) was detected at 60 dpv, in all vaccinated animals. After challenge all vaccinated dogs remained healthy for 180 days. Control animals (unvaccinated dogs) developed symptoms of rabies on day 6 post administration of a virulent virus and died of rabies on days 11-13. Of note, the VNA titers in all the wild carnivores (corsacs and wolves) immunized with VRC-RZ2 were higher than 0.5 IU/ml (0.59 ± 0.11 IU/ml), even as early as 14 days post vaccination. These, presumably protective, titers of antibodies to rabies virus were present in the dogs and wild carnivores examined in this study for at least 180 days.

The Role of the Gray Wolf in Rabies Transmission in Iran and Preliminary Assessment of an Oral Rabies Vaccine in this Animal

“…The V-RG ® recombinant vaccine showed a great promise as an oral vaccine for wildlife during the 1980s when the experiments were conducted on captive raccoons and foxes [32]. Unlike similar studies on ORVs [19], in our study, seroconversion was not observed until two weeks. However, the level of anti-rabies antibodies after seroconversion remained over 0.5 IU/ml in all vaccinated wolves suggesting the efficacy of Raboral V-RG ® as an effective vaccine for wolves.…”

“…The oral bait vaccines can be distributed over extensive areas in a short period. Until now, several strains of rabies vaccine baits have been developed and applied to the wildlife worldwide [18,19], and the WHO has approved some oral vaccine baits for rabies control in wildlife [20]. For example, according to the EU requirements, the SAG2 baits were efficient for vaccination of the red fox and raccoon dog, and Raboral V-RG ® has been widely used to control rabies in foxes and raccoons [21,22].…”

Oral vaccination of dogs: a well-studied and undervalued tool for achieving human and dog rabies elimination

“…rERAG333E is a recombinant ERA rabies virus strain containing a mutation from Arg to Glu at G333 position [ 31 ]. Other live-attenuated recombinant rabies virus vaccines (RV SN10-333; RV SPBN-Cyto c; RV SPBNGAS; RV SPBNGAS-GAS; VRC-RZ2) were also tested in dogs [ 26 , 32 , 33 ].…”

“…According to European Pharmacopoeia and the US Code of Federal Regulations, efficacy of inactivated vaccines for dogs must be demonstrated by challenge at the end of the immunity period claimed by the manufacturer (generally 1 year using 25 vaccinates and 10 controls). Three oral vaccine candidates have been evaluated in dogs with a challenge performed 6 months (SAG2 [ 22 ] and VRC-RZ2 [ 33 ]) and 2 years (CAV-2-E3Δ-RGP [ 30 ]) after vaccine bait administration.…”

2018 international meeting of the Global Virus Network

“…vaccination intervals and bait densities) (Sterner et al, 2009)s and vaccine strain (e.g. minimal effective ORV dose and uptake differs per species) (Zhugunissov et al, 2017).…”