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The objective of this study was to evaluate the bait preference of three selected bait types by local dogs and the induced immunogenicity of the oral rabies vaccine strain SPBN GASGAS in Morocco. The vaccine strain, combined with different bait types, has been tested in many different settings, but not yet in northern Africa. Overall, bait consumption and preference were similar in other studies using the same materials (bait type and sachet). The intestine bait had the highest acceptance rate (97.6%, 95%CI: 87.4–99.9), followed by the egg bait (83.0%, 95%CI: 69.2–92.4). Only 52% (95%CI: 37.4–66.3) of the dogs showed an interest in the fish meal bait. However, considering the successful release of the contents of the sachet (blue-dyed water) into the oral cavity, the egg bait (65.7%, 95%CI: 47.8–80.9) scored better than the intestine bait (51.7%, 95%CI: 32.5–70.6). The dogs selected for the immunogenicity study were offered the egg bait containing a sachet filled with SPBN GASGAS (3.0 mL, 107.5 FFU/mL) or were given the same dose by direct oral administration (d.o.a.). In addition, several dogs were vaccinated by the parenteral route (s.c.) using a commercially available inactivated rabies vaccine. Unfortunately, due to the COVID-19 pandemic and subsequent travel restrictions, it was not possible to collect blood samples directly after vaccination. The blood samples were collected pre-vaccination and on five occasions between 450 and 1088 days post vaccination. The seroconversion rate, as determined for rabies-virus-neutralizing antibodies by the FAVN test, was significantly lower than that found for binding antibodies, as determined by ELISA, for all blood samples collected post vaccination. No treatment effect (bait, d.o.a., s.c.) could be seen in the seroconversion rate. At 15 months post vaccination, 84.2% of the dogs offered vaccine bait still tested sero-positive in ELISA. Only after 3 years was a clear drop in the seroconversion rate observed in all three treatment groups. This study confirms the long-term immunogenicity of the oral rabies vaccine SPBN GASGAS in dogs under field conditions.

In a long-term immunogenicity study (1100 days post vaccination) in local Thai dogs the immune response of the oral rabies vaccine SPBN GASGAS was compared to those elicited by a commercial inactivated vaccine using immunobridging. Based on the detection of rabies virus binding (rVBA) and rabies virus neutralizing antibodies (rVNA) as measured by ELISA and Rapid Fluorescent Focus Inhibition Test (RFFIT) the long-term immune response in dogs vaccinated orally with the SPBNA GASGAS strain of rabies vaccine in a bait was non-inferior to a conventional inactivated rabies vaccine. The outcome of this study supports extending the originally claimed duration of immunity (DOI) of SPBN GASGAS after oral vaccination for dogs from 6 to 30 months.

Dog-mediated rabies is endemic in much of Indonesia, including Bali. Most dogs in Bali are free-roaming and often inaccessible for parenteral vaccination without special effort. Oral rabies vaccination (ORV) is considered a promising alternative to increase vaccination coverage in these dogs. This study assessed immunogenicity in local dogs in Bali after oral administration of the highly attenuated third-generation rabies virus vaccine strain SPBN GASGAS. Dogs received the oral rabies vaccine either directly or by being offered an egg-flavored bait that contained a vaccine-loaded sachet. The humoral immune response was then compared with two further groups of dogs: a group that received a parenteral inactivated rabies vaccine and an unvaccinated control group. The animals were bled prior to vaccination and between 27 and 32 days after vaccination. The blood samples were tested for the presence of virus-binding antibodies using ELISA. The seroconversion rate in the three groups of vaccinated dogs did not differ significantly: bait: 88.9%; direct-oral: 94.1%; parenteral: 90.9%; control: 0%. There was no significant quantitative difference in the level of antibodies between orally and parenterally vaccinated dogs. This study confirms that SPBN GASGAS is capable of inducing an adequate immune response comparable to a parenteral vaccine under field conditions in Indonesia. [ABSTRACT FROM AUTHOR]

Dog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging for various reasons. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. While oral rabies vaccination (ORV) of dogs is primarily considered a tool to increase herd immunity, particularly by targeting free-roaming and stray dogs, here, we are showcasing an ORV-only approach as an emergency response model. Using a third-generation vaccine and a standardized egg-flavored bait, we assessed the effectiveness and vaccination under field conditions in the Zambezi region of Namibia. During this trial, with four teams and within four working days, 3097 dogs were offered a bait, of which 88,0% were considered vaccinated. Teams managed to vaccinate, on average, over 20 dogs/h, despite using a door-to-door vaccination approach.The favorable results both in terms of bait acceptance and successful vaccination as well as field applicability and effectiveness further support the great potential of ORV in dog rabies control programmes.

(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity and efficacy of the third-generation oral rabies virus vaccine strain, SPBN GASGAS, in domestic dogs, dogs were offered an egg-flavoured bait containing 3.0 mL of the vaccine (107.5 FFU/mL) or a placebo egg-flavoured bait. Subsequently, these 25 vaccinated and 10 control animals were challenged approximately 6 months later with a dog rabies virus isolate. Blood samples were collected at different time points postvaccination and examined by ELISA and RFFIT. (3) Results: All but 1 of the 25 vaccinated dogs survived the challenge infection; meanwhile, all 10 control dogs succumbed to rabies. The serology results showed that all 25 vaccinated dogs seroconverted in ELISA (>40% PB); meanwhile, only 13 of the 25 vaccinated dogs tested seropositive ≥ 0.5 IU/mL) in RFFIT. (4) Conclusions: The SPBN GASGAS rabies virus vaccine meets the efficacy requirements for live oral rabies vaccines as laid down by the European Pharmacopoeia and the WOAH Terrestrial Manual. SPBN GASGAS already fulfilled the safety requirements for oral rabies vaccines targeted at dogs. Hence, the egg-flavoured bait containing SPBN GASGAS is the first oral vaccine bait that complies with WOAH recommendations for the intended use of oral vaccination of free-roaming dogs against rabies. [ABSTRACT FROM AUTHOR]

(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity and efficacy of the third-generation oral rabies virus vaccine strain, SPBN GASGAS, in domestic dogs, dogs were offered an egg-flavoured bait containing 3.0 mL of the vaccine (107.5 FFU/mL) or a placebo egg-flavoured bait. Subsequently, these 25 vaccinated and 10 control animals were challenged approximately 6 months later with a dog rabies virus isolate. Blood samples were collected at different time points postvaccination and examined by ELISA and RFFIT. (3) Results: All but 1 of the 25 vaccinated dogs survived the challenge infection; meanwhile, all 10 control dogs succumbed to rabies. The serology results showed that all 25 vaccinated dogs seroconverted in ELISA (>40% PB); meanwhile, only 13 of the 25 vaccinated dogs tested seropositive ≥ 0.5 IU/mL) in RFFIT. (4) Conclusions: The SPBN GASGAS rabies virus vaccine meets the efficacy requirements for live oral rabies vaccines as laid down by the European Pharmacopoeia and the WOAH Terrestrial Manual. SPBN GASGAS already fulfilled the safety requirements for oral rabies vaccines targeted at dogs. Hence, the egg-flavoured bait containing SPBN GASGAS is the first oral vaccine bait that complies with WOAH recommendations for the intended use of oral vaccination of free-roaming dogs against rabies.

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.

Abstract Background Oral vaccination of the small Indian mongoose against rabies has been suggested as a potential tool to eliminate mongoose-mediated rabies on several Caribbean islands. A recently developed oral rabies virus vaccine strain, SPBN GASGAS, has already been shown to be efficacious in this reservoir species. Since, all available oral rabies vaccines are based on replication-competent viruses and vaccine baits are distributed unsupervised in the environment, enhanced safety standards for such vaccine types are required. Results The results of safety studies, including overdose, repeated doses, dissemination and different routes of administration, in the target species are presented. It was shown that the construct was apathogenic, irrespective of dose and route of administration. Even when it was inoculated directly in the brain, it did not induce rabies infection. Furthermore, the vaccine strain did not spread within the target species after direct oral instillation beyond the site of entry. Conclusion The vaccine strain SPBN GASGAS meets the safety requirements for live rabies virus vaccines in this target species, the small Indian mongoose.

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

Applied research is crucial in pushing the boundaries and finding a solution to the age-old problem of dog-mediated rabies. Although oral vaccination of dogs is considered to have great potential in mass dog vaccination campaigns and could have far-reaching benefits, it is perhaps the most ignored of all available tools in efforts to eliminate dog-mediated rabies, not least because of limited data on immunogenicity, efficacy, and safety of potential oral rabies vaccine candidates. In this study, the long-term immunogenicity in local Thai dogs after oral administration of the highly attenuated 3rd generation rabies virus vaccine strain SPBN GASGAS was assessed. The oral rabies vaccine was administered to dogs by either direct oral administration (n = 10) or by offering a vaccine loaded intestine bait (n = 15). The humoral immune response was then compared to three groups of dogs; a group that received a parenteral delivered inactivated rabies vaccine (n = 10), a group offered a placebo intestine bait (n = 7), and a control group (n = 4) for an observation period of 365 days. There was no significant difference in the immune response of dogs that received oral and parenteral vaccine in terms of magnitude, kinetics, and persistence of both rabies virus (RABV) neutralizing (RFFIT) and binding (ELISA) antibodies. Although the single parenteral injection of an inactivated rabies vaccine mounted a slightly higher humoral immune response than the orally delivered live vaccine, RABV specific antibodies of both types were still detectable after one year in most animals for all treatment groups and resulted in no difference in seropositivity. Characterization of rabies specific antibodies revealed two main classes of antibodies involved in the immune response of dogs vaccinated. While IgM antibodies were the first to appear, the succeeding IgG response was mainly IgG2 dominated independent of the vaccine type used. The results support the view that SPBN GASGAS induces a sustained detectable immune response in local dogs both after direct oral administration and via bait application.

In order to obtain Marketing Authorization for an oral rabies vaccine in the European Union, not only safety studies in the target species, red fox and raccoon dog, are required. Since baits are distributed unsupervised in the environment, specific safety studies in selected non-target species are compulsory. Furthermore, oral rabies vaccines are based on live, replication-competent viruses and thus distinct safety studies in the target species for such type of vaccines are also mandatory. Here, the results of these safety studies in target and selected non-target species for a 3rd generation oral rabies virus vaccine construct, SPBN GASGAS (Rabitec), are presented. The studies included the following species; red fox, raccoon dog, domestic dog, domestic cat, domestic pig, wild rodents. The following safety topics were investigated; overdose, repeated dose, dissemination, shedding, horizontal and vertical transmission. It was shown that SPBN GASGAS did not cause disease or any other adverse reaction in vaccinated animals and naïve contact animals. The vaccine did not disseminate within the host beyond the site of entry. No horizontal transmission was observed in wild rodents. In the target species, there was evidence that in a few cases horizontal transmission of vaccine virus could have occurred under these experimental conditions; most likely immediately after vaccine administration. The vaccine construct SPBN GASGAS meets therefore the latest revised minimal safety requirements as laid down in the European Pharmacopoeia.

A safety requirement for live vaccines is investigating possible shedding in recipients since the presence of replication competent vaccine in secretions could result in direct and indirect horizontal transmission. This is especially relevant for oral rabies vaccine baits that are deliberately distributed into the environment. In the current study, survival of an oral rabies virus vaccine, SPBN GASGAS, was examined in excretions from different target and non-target species; red fox, raccoon dog, small Indian mongoose, raccoon, striped skunk, domestic dog, domestic cat and domestic pig. Saliva – and (pooled) fecal samples collected at different time points after oral administration of the vaccine strain were examined for the presence of viral RNA (rt-PCR). All PCR-positive and a subset of PCR-negative samples were subsequently investigated for the presence of infectious virus by isolation in cell culture (RTCIT). Up to 7 days post vaccine administration viral RNA could be detected in 50 of 758 fecal samples but no infectious virus was detected in any of the examined PCR-positive fecal samples. In contrast, RNA-fragments were detected in 248 of 1053 saliva swabs for an extended period (up to 10 days) after vaccine administration, but viable virus was only present during the first hours post vaccine administration in 38 samples. No infectious vaccine virus was isolated in saliva swabs taken 24 h or more after vaccine administration. Hence, no active shedding of the vaccine virus SPBN GASGAS after oral administration occurred and the virus isolated during the initial hours was material originally administered and not a result of virus replication within the host. Thus, potential horizontal transmission of this vaccine virus is limited to a short period directly after vaccine bait uptake. It can be concluded that the environmental risks associated with shedding after distributing vaccine baits containing SPBN GASGAS are negligible. [ABSTRACT FROM AUTHOR]

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species. [ABSTRACT FROM AUTHOR]

Applied research is crucial in pushing the boundaries and finding a solution to the age-old problem of dog-mediated rabies. Although oral vaccination of dogs is considered to have great potential in mass dog vaccination campaigns and could have far-reaching benefits, it is perhaps the most ignored of all available tools in efforts to eliminate dog-mediated rabies, not least because of limited data on immunogenicity, efficacy, and safety of potential oral rabies vaccine candidates. In this study, the long-term immunogenicity in local Thai dogs after oral administration of the highly attenuated 3rd generation rabies virus vaccine strain SPBN GASGAS was assessed. The oral rabies vaccine was administered to dogs by either direct oral administration (n = 10) or by offering a vaccine loaded intestine bait (n = 15). The humoral immune response was then compared to three groups of dogs; a group that received a parenteral delivered inactivated rabies vaccine (n = 10), a group offered a placebo intestine bait (n = 7), and a control group (n = 4) for an observation period of 365 days. There was no significant difference in the immune response of dogs that received oral and parenteral vaccine in terms of magnitude, kinetics, and persistence of both rabies virus (RABV) neutralizing (RFFIT) and binding (ELISA) antibodies. Although the single parenteral injection of an inactivated rabies vaccine mounted a slightly higher humoral immune response than the orally delivered live vaccine, RABV specific antibodies of both types were still detectable after one year in most animals for all treatment groups and resulted in no difference in seropositivity. Characterization of rabies specific antibodies revealed two main classes of antibodies involved in the immune response of dogs vaccinated. While IgM antibodies were the first to appear, the succeeding IgG response was mainly IgG2 dominated independent of the vaccine type used. The results support the view that SPBN GASGAS induces a sustained detectable immune response in local dogs both after direct oral administration and via bait application. [ABSTRACT FROM AUTHOR]

Background: Oral vaccination of the small Indian mongoose against rabies has been suggested as a potential tool to eliminate mongoose-mediated rabies on several Caribbean islands. A recently developed oral rabies virus vaccine strain, SPBN GASGAS, has already been shown to be efficacious in this reservoir species. Since, all available oral rabies vaccines are based on replication-competent viruses and vaccine baits are distributed unsupervised in the environment, enhanced safety standards for such vaccine types are required. Results: The results of safety studies, including overdose, repeated doses, dissemination and different routes of administration, in the target species are presented. It was shown that the construct was apathogenic, irrespective of dose and route of administration. Even when it was inoculated directly in the brain, it did not induce rabies infection. Furthermore, the vaccine strain did not spread within the target species after direct oral instillation beyond the site of entry. Conclusion: The vaccine strain SPBN GASGAS meets the safety requirements for live rabies virus vaccines in this target species, the small Indian mongoose. [ABSTRACT FROM AUTHOR]