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.

Introduction: To achieve the global goal of canine-mediated human rabies elimination by 2030 there is an urgent need to scale-up mass dog vaccination activities in regions with large dog populations that are difficult to access; a common situation in much of India. Oral rabies vaccination may enable the vaccination of free-roaming dogs that are inaccessible to parenteral vaccination, and is considered a promising complementary measure to parenteral mass dog vaccination campaigns. WHO and OIE have published detailed minimum requirements for rabies vaccines and baits to be used for this purpose, requiring that baits must not only be well-accepted by the target population but must also efficiently release the vaccine in the oral cavity. For oral rabies vaccination approaches to be successful, it is necessary to develop baits which have a high uptake by the target population, are culturally accepted and amenable to mass production. The aim of this study was to compare the interest and uptake rates of meat-based and an egg-based prototype bait constructs by free roaming dogs in Goa, India. Methods: Three teams randomly distributed two prototype baits; an egg-flavoured bait and a commercial meat dog food (gravy) flavoured bait. The outcomes of consumption were recorded and compared between baits and dog variables. Results: A total of 209 egg-bait and 195 gravy-bait distributions were recorded and analysed. No difference (p = 0.99) was found in the percentage of dogs interested in the baits when offered. However, significantly more dogs consumed the egg-bait than the gravy-bait; 77.5% versus 68.7% (p = 0.04). The release of the blue-dyed water inside the sachet in the oral cavity of the animals was significant higher in the dogs consuming an egg-bait compared to the gravy-bait (73.4% versus 56.7%, p = 0.001). Conclusions: The egg-based bait had a high uptake amongst free roaming dogs and also enabled efficient release of the vaccine in the oral cavity, whilst also avoiding culturally relevant materials of bovine or porcine meat products.

: To evaluate the long-term immunogenicity of the live-attenuated, oral rabies vaccine SPBN GASGAS in a full good clinical practice (GCP) compliant study, forty-six (46) healthy, seronegative red foxes (Vulpes vulpes) were allocated to two treatment groups: group 1 (n = 31) received a vaccine bait containing 1.7 ml of the vaccine of minimum potency (106.6 FFU/mL) and group 2 (n = 15) received a placebo-bait. In total, 29 animals of group 1 and 14 animals of group 2 were challenged at 12 months post-vaccination with a fox rabies virus isolate (103.0 MICLD50/mL). While 90% of the animals offered a vaccine bait resisted the challenge, only one animal (7%) of the controls survived. All animals that had seroconverted following vaccination survived the challenge infection at 12 months post-vaccination. Rabies specific antibodies could be detected as early as 14 days post-vaccination. Based on the kinetics of the antibody response to SPBN GASGAS as measured in ELISA and RFFIT, the animals maintained stable antibody titres during the 12-month pre-challenge observation period at a high level. The results indicate that successful vaccination using the oral route with this new rabies virus vaccine strain confers long-term duration of immunity beyond one year, meeting the same requirements as for licensure as laid down by the European Pharmacopoeia.

ABSTRACT:The small Indian mongoose (Herpestes auropunctatus), a rabies reservoir species on several Islands in the Caribbean, was successfully immunized against rabies for the first time by offering animals a vaccine bait specifically designed for this small carnivore. The bait contained on average 0.6 mL of the genetically modified replication-competent rabies virus construct SPBN GASGAS (10 8.5 focus-forming units/mL). Three of four mongooses offered a bait developed an immune response above 0.5 IU/mL, but the response was less pronounced than in two animals offered the vaccine by direct oral instillation.

Dog-mediated rabies is endemic throughout Africa. While free-roaming dogs that play a crucial role in rabies transmission are often inaccessible for parenteral vaccination during mass dog vaccination campaigns, oral rabies vaccination (ORV) is considered to be a promising alternative to increase vaccination coverage in these hard-to-reach dogs. The acceptance of ORV as an efficient supplementary tool is still low, not least because of limited immunogenicity and field trial data in local dogs. In this study, the immunogenicity of the highly attenuated 3rd-generation oral rabies vaccine strain SPBN GASGAS in local free-roaming dogs from Namibia was assessed by determining the immune response in terms of seroconversion for up to 56 days post-vaccination. At two study sites, free-roaming dogs were vaccinated by administering the vaccine either by direct oral administration or via a vaccine-loaded egg bait. Pre- and post-vaccination blood samples were tested for rabies virus neutralizing as well as binding antibodies using standard serological assays. A multiple logistic regression (MLR) analysis was performed to determine a possible influence of study area, vaccination method, and vaccine dose on the seroconversion rate obtained. About 78% of the dogs vaccinated by the oral route seroconverted (enzyme-linked immunosorbent assay, ELISA), though the seroconversion as determined by a rapid fluorescence focus inhibition test (RFFIT) was much lower. None of the factors examined had a significant effect on the seroconversion rate. This study confirms the immunogenicity of the vaccine strain SPBN GASGAS and the potential utility of ORV for the control of dog-mediated rabies in African dogs.