Evaluation of immune responses in dogs to oral rabies vaccine under field conditions.
ABSTRACT: During the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. However, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. Alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (ORV). In 2016, a traditional mass dog vaccination campaign in Haiti was supplemented with ORV to improve vaccination coverage and to evaluate the use of ORV in dogs. Blisters containing live-attenuated, vaccine strain SPBNGAS-GAS were placed in intestine bait and distributed to dogs by hand. Serum was collected from 107 dogs, aged 3-12 months with no reported prior rabies vaccination, pre-vaccination and from 78/107 dogs (72.9%) 17 days post-vaccination. The rapid florescent focus inhibition test (RFFIT) was used to detect neutralizing antibodies and an ELISA to detect rabies binding antibodies. Post-vaccination, 38/41 (92.7%) dogs that received parenteral vaccine had detectable antibody (RFFIT >0.05?IU/mL), compared to 16/27 (59.3%, p?40% blocking, p?0.05?IU/mL) were detected in 10/107 reportedly vaccine-naïve dogs (9.3%). Parenteral vaccination remains the most reliable method for ensuring adequate immune response in dogs, however ORV represents a viable strategy to supplement existing parental vaccination campaigns in hard-to-reach dog populations. The hand-out model reduces the risk of unintended contact with ORV through minimizing vaccine blisters left in the community.
Project description: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 (<i>n</i> = 10) or by offering a vaccine loaded intestine bait (<i>n</i> = 15). The humoral immune response was then compared to three groups of dogs; a group that received a parenteral delivered inactivated rabies vaccine (<i>n</i> = 10), a group offered a placebo intestine bait (<i>n</i> = 7), and a control group (<i>n</i> = 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.
Project description:Mass parenteral vaccination remains the cornerstone of dog rabies control. Oral rabies vaccination (ORV) could increase vaccination coverage where free-roaming dogs represent a sizeable segment of the population at risk. ORV's success is dependent on the acceptance of baits that release an efficacious vaccine into the oral cavity. A new egg-flavored bait was tested alongside boiled bovine intestine and a commercially available fishmeal bait using a hand-out model on the Navajo Nation, United States, during June 2016. A PVC capsule and biodegradable sachet were tested, and had no effect on bait acceptance. The intestine baits had the highest acceptance (91.9%; 95% confidence interval (CI), 83.9%?96.7%), but the fishmeal (81.1%; 95% CI, 71.5%?88.6%) and the egg-flavored baits (77.4%; 95% CI, 72.4%?81.8%) were also well accepted, suggesting that local bait preference studies may be warranted to enhance ORV's success in other areas where canine rabies is being managed. Based on a dyed water marker, the delivery of a placebo vaccine was best in the intestine baits (75.4%; 95% CI, 63.5%?84.9%), followed by the egg-flavored (68.0%; 95% CI, 62.4%?73.2%) and fishmeal (54.3%; 95% CI, 42.9%?65.4%) baits. Acceptance was not influenced by the supervision or ownership, or sex, age, and body condition of the dogs. This study illustrates that a portion of a dog population may be orally vaccinated as a complement to parenteral vaccination to achieve the immune thresholds required to eliminate dog rabies.
Project description:The statistics of rabies cases in Volyn, Lviv, and Zakarpattia oblasts of Ukraine from 2012 to 2016 were analyzed to establish spatial-temporal distribution of rabies endemic outbreaks and to identify causes of widespread infections among wild and domestic animals. The occurrence of rabies outbreaks in wild and domestic animals in Ukraine was also assessed to determine the effectiveness of oral rabies vaccination (ORV) efforts. According to our analysis, parenteral vaccination of domestic animals and ORV campaigns in foxes have proved unsuccessful in providing a sustainable, long-term reduction in endemic rabies outbreaks. ORV campaigns in foxes were deemed ineffective based on our studies of the endemic rabies outbreaks in Volyn, Lviv, and Zakarpattia oblasts in 2012-2016. The current rabies prevention system (parenteral vaccination) failed to offer protection to domestic animals based on our review of the occurrence of endemic rabies outbreaks in dogs and cats. ORV campaign shortcomings and their causes must be identified in order to provide maximum rabies vaccine coverage for dogs and cats. Altogether, the results presented here provide information that can assist public health agencies to devise more effective disease control plans to curtail the spread of rabies in domestic animals and wildlife in Ukraine.
Project description:Rabies is a fatal zoonosis that still causes nearly 70, 000 human deaths every year. In Europe, the oral rabies vaccination (ORV) of red foxes (Vulpes vulpes) was developed in the late 1970s and has demonstrated its effectiveness in the eradication of the disease in Western and some Central European countries. Following the accession of the three Baltic countries--Estonia, Latvia and Lithuania--to the European Union in 2004, subsequent financial support has allowed the implementation of regular ORV campaigns since 2005-2006. This paper reviews ten years of surveillance efforts and ORV campaigns in these countries resulting in the near eradication of the disease. The various factors that may have influenced the results of vaccination monitoring were assessed using generalized linear models (GLMs) on bait uptake and on herd immunity. As shown in previous studies, juveniles had lower bait uptake level than adults. For the first time, raccoon dogs (Nyctereutes procyonoides) were shown to have significantly lower bait uptake proportion compared with red foxes. This result suggests potentially altered ORV effectiveness in this invasive species compared to the red foxes. An extensive phylogenetic analysis demonstrated that the North-East European (NEE) rabies phylogroup is endemic in all three Baltic countries. Although successive oral vaccination campaigns have substantially reduced the number of detected rabies cases, sporadic detection of the C lineage (European part of Russian phylogroup) underlines the risk of reintroduction via westward spread from bordering countries. Vaccine induced cases were also reported for the first time in non-target species (Martes martes and Meles meles).
Project description:<i>Introduction:</i> 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. <i>Methods:</i> 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. <i>Results</i>: A total of 209 egg-bait and 195 gravy-bait distributions were recorded and analysed. No difference (<i>p</i> = 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% (<i>p</i> = 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%, <i>p</i> = 0.001). <i>Conclusions</i>: 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.
Project description:The mass vaccination of dogs is a proven tool for rabies prevention. Besides parenteral delivery of inactivated vaccines, over the past several decades, several self-replicating biologics, including modified-live, attenuated and recombinant viruses, have been evaluated for the oral vaccination of dogs against rabies. Vaccines are included within an attractive bait for oral consumption by free-ranging dogs. Due to the high affinity between dogs and humans, such biologics intended for oral vaccination of dogs (OVD) need to be efficacious as well as safe. Baits should be preferentially attractive to dogs and not to non-target species. Although many different types have been evaluated successfully, no universal bait has been identified to date. Moreover, high bait acceptance does not necessarily mean that vaccine efficacy and programmatic success is predictable. The use of OVD in the laboratory and field has demonstrated the safety and utility of this technology. Within a One Health context, OVD should be considered as part of a holistic plan for the global elimination of canine rabies.
Project description:Oral rabies vaccination (ORV) is highly effective in foxes and raccoon dogs, whereas for unknown reasons the efficacy of ORV in other reservoir species is less pronounced. To investigate possible variations in species-specific cell tropism and local replication of vaccine virus, different reservoir species including foxes, raccoon dogs, raccoons, mongooses, dogs and skunks were orally immunised with a highly attenuated, high-titred GFP-expressing rabies virus (RABV). Immunofluorescence and RT-qPCR screenings revealed clear differences among species suggesting host specific limitations to ORV. While for responsive species the palatine tonsils (tonsilla palatina) were identified as a main site of virus replication, less virus dissemination was observed in the tonsils of rather refractory species. While our comparison of vaccine virus tropism emphasizes the important role that the tonsilla palatina plays in eliciting an immune response to ORV, our data also indicate that other lymphoid tissues may have a more important role than originally anticipated. Overall, these data support a model in which the susceptibility to oral live RABV vaccine infection of lymphatic tissue is a major determinant in vaccination efficacy. The present results may help to direct future research for improving vaccine uptake and efficacy of oral rabies vaccines under field conditions.
Project description:Despite the implementation of control measures (preventive dog vaccination), rabies has become endemic in Croatia, with red foxes being the main reservoir species. Oral rabies vaccination (ORV) campaigns supported by the European Commission have been conducted twice a year since the spring of 2011. The first campaigns were limited to the northern and eastern parts of the country, and from the autumn of 2012, the program was extended to the entire country. The Lysvulpen vaccine containing the SAD Bern strain was used for ORV. Following the vaccination campaigns, the number of rabies cases decreased, and the last positive case was recorded in February 2014. The bait uptake ranged from 24.86% to 84.62% and the immunisation rate from 11.24% to 35.64%.
Project description:: 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.
Project description:BACKGROUND: Oral rabies vaccination (ORV) in rabies infected regions should target the primary rabies vector species, which in Lithuania includes raccoon dogs as well as red foxes. Specific investigations on ORV in raccoon dogs are needed e.g. evaluation of vaccine effectiveness under field conditions. The objective of the current study was to investigate the efficacy of the ORV programme 2006-2010 in Lithuania by examining the number of rabies cases and estimating the prevalences of a tetracycline biomarker (TTC) and rabies virus antibodies in raccoon dogs. METHODS: From 2006 to 2010, 12.5 million rabies vaccine-baits were distributed by aircraft. Baiting occurred twice per year (spring and autumn), targeting raccoon dogs and red foxes in a 63,000 km2 area of Lithuania. The mandibles of raccoon dogs found dead or killed in the vaccination area were analyzed by fluorescence microscopy for the presence of the TTC. Rabies virus sera neutralizing anti-glycoprotein antibody titres were determined using an indirect ELISA method and seroconversion (> 0.5 EU/ml) rates were estimated. RESULTS: During the study period, 51.5% of raccoon dog mandibles were positive for TTC. 1688 of 3260 tested adults and 69 of 175 tested cubs were TTC positive. Forty-seven percent of raccoon dog serum samples were positive for rabies virus antibodies. 302 of 621 investigated adults and 33 of 95 investigated cubs were seropositive. In the same time 302 of 684 and 43 of 124 tested samples were TTC and ELISA positive in spring; whereas 1455 of 2751 and 292 of 592 tested samples were TTC and ELISA positive in autumn. There was a positive correlation between the number of TTC and antibody positive animals for both adult and cub groups. CONCLUSIONS: ORV was effective in reducing the prevalence of rabies in the raccoon dog population in Lithuania. The prevalence of rabies cases in raccoon dogs in Lithuania decreased from 60.7% in 2006-2007 to 6.5% in 2009-2010.