Efficacy of the oral rabies virus vaccine strain SPBN GASGAS in foxes and raccoon dogs

Abstract

To test the immunogenicity and efficacy of a new oral rabies virus vaccine strain SPBN GASGAS in wildlife target species, one group of foxes and two groups of raccoon dogs were offered a bait containing 1.7 ml of the vaccine (10 FFU/ml; 10 FFU/dose) and subsequently challenged approximately 180 days later with a fox rabies virus isolate. One group of raccoon dogs (n=30) received the same challenge dose (10 MICLD/ml) as the red foxes (n=29). The other group with raccoon dogs (n=28) together with 8 animals that received the vaccine dose by direct instillation into the oral cavity (DIOC) were infected with a 40-fold higher dose of the challenge virus (10 MICLD/ml). All but one of the 29 vaccinated foxes survived the challenge infection; meanwhile all 12 control foxes succumbed to rabies. Twenty-eight of 30 vaccinated raccoon dogs challenged with the same dose survived the infection, however only six of 12 control animals succumbed. When the higher challenge dose was administered, all 12 control animals died from rabies and all 36 vaccinated animals (28 baited plus 8 DIOC) survived. Blood samples were collected at different time points post vaccination and examined by both RFFIT and ELISA. The kinetics of the measured immune response was similar for both species, although in RFFIT slightly higher values were observed in foxes than in raccoon dogs. However, the immune response as measured in ELISA was identical for both species. The oral rabies virus vaccine SPBN GASGAS meets the efficacy requirements for live rabies virus vaccines as laid down by the European Pharmacopoeia.

Experimental screening studies on rabies virus transmission and oral rabies vaccination of the Greater Kudu (Tragelaphus strepsiceros)

“…While the relatively short incubation periods of 12–26 days observed after high dose infection are within the lower bounds of the expected range and are comparable to those of carnivorous reservoir species, Kudus and cattle 12 , 19 , 31 – 34 , the extremely long incubation periods of 93–245 days after low dose infection are remarkable, particularly against the background of the same route of infection and the fact that the difference in viral dose was just two log 10 steps (Fig. 4 ).…”

“…However, it is the first time that such a proof-of-concept study has ever been conducted in an herbivorous species such as Kudus. The vaccine strain SPBN GASGAS has shown to be efficacious in several animal species like red foxes ( Vulpes vulpes ), raccoon dogs ( Nyctereutes procyonoides ), raccoon ( Procyon lotor ) and small Indian mongoose ( Herpestes auropunctatus ) 19 , 52 , 53 . However, striped skunks ( Mephitis mephitis ) seem to be rather refractory to vaccination through the oral route in a vaccine virus titer dependent manner 47 .…”

“…For DOA an oral vaccine virus strain with a very high safety profile was used. The vaccine strain SPBN GASGAS licensed for foxes and raccoon dogs 19 is derived from SAD L16, a cDNA clone of the oral RABV vaccine strain SAD B19. SPBN GASGAS lacks the pseudogene (ψ) and contains an additional identical RABV glycoprotein (G) which both show alterations at amino acid positions 194 and 333; position 194-AAT [Asn] → TCC [Ser], position 333-AGA [Arg] → GAG [Glu] 20 .…”

In Vivo Safety Studies With SPBN GASGAS in the Frame of Oral Vaccination of Foxes and Raccoon Dogs Against Rabies

“…It can be concluded that the oral rabies virus vaccine SPBN GASGAS meets the latest revised safety requirements of the European Pharmacopoeia ( 1 ). The efficacy of this vaccine strain in the target species, red fox and raccoon dog, has been previously shown ( 32 ). Hence, this third generation oral rabies virus vaccine has retained the immunogenic properties of its parental strain SAD B19 but has a greatly improved safety profile in comparison to first and second generation oral rabies virus vaccines.…”

Hepatitis E virus (HEV)—The Future

“…In the case of free range farms, animals should be protected from infection by wild boars, e.g., by a solid wall. Possibly, in far future HEV can be controlled and eliminated from the wild animals using oral vaccination as was successfully done in oral rabies vaccination campaigns for foxes and raccoon dogs [77]. In addition to wild boars, other wild animals can be HEV-positive and can transmit the virus.…”