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The original article [1] contained an error in the Author details paragraph. " 5 Neglected Zoonotic Diseases, World Health Organization, Geneva, Switzerland" should be replaced by " 5 Le Grand-Saconnex, Switzerland".

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.

RABORAL V-RG ® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Safety of V-RG has been evaluated in over 50 vertebrate species, including non-human primates, with no adverse effects observed regardless of route or dose. Immunogenicity and efficacy have been demonstrated under laboratory and field conditions in multiple target species (including fox, raccoon, coyote, skunk, raccoon dog, and jackal). The liquid vaccine is packaged inside edible baits (i.e., RABORAL V-RG, the vaccine-bait product) which are distributed into wildlife habitats for consumption by target species. Field application of RABORAL V-RG has contributed to the elimination of wildlife rabies from three European countries (Belgium, France and Luxembourg) and of the dog/coyote rabies virus variant from the United States of America (USA). An oral rabies vaccination program in west-central Texas has essentially eliminated the gray fox rabies virus variant from Texas with the last case reported in a cow during 2009. A long-term ORV barrier program in the USA using RABORAL V-RG is preventing substantial geographic expansion of the raccoon rabies virus variant. RABORAL V-RG has also been used to control wildlife rabies in Israel for more than a decade. This paper: (1) reviews the development and historical use of RABORAL V-RG; (2) highlights wildlife rabies control programs using the vaccine in multiple species and countries; and (3) discusses current and future challenges faced by programs seeking to control or eliminate wildlife rabies.

The SAG2 vaccine (RABIGEN® SAG2) is a modified live attenuated rabies virus vaccine, selected from the SAD Bern strain in a two-step process of amino acid mutation using neutralizing monoclonal antibodies. The strain is genetically stable and does not spread in vivo or induce a persistent infection. Its absence of residual pathogenicity was extensively demonstrated in multiple target and non target species (such as wild carnivores and rodent species), including non-human primates. The efficacy of SAG2 baits was demonstrated according to the EU requirements for the red fox and raccoon dog. The use of safe and potent rabies vaccines such as SAG2 largely contributed to the elimination of rabies in Estonia, France, Italy and Switzerland. Importantly, these countries were declared free of rabies after few years of oral vaccination campaigns with SAG2 baits distributed with an appropriate strategy. The excellent tolerance of the SAG2 vaccine has been confirmed in the field since its first use in 1993. No safety issues have been reported, and in particular no vaccine-induced rabies cases were diagnosed, after the distribution of more than 20 million SAG2 baits in Europe.

During the spring of 1997, various protocols of rabies vaccine bait (SAG2) distribution for foxes were compared: in the first test zone, a first distribution was organised at the end of April, followed by a second distribution two weeks later; in the second test zone, there was a first distribution at the same period as for the previous zone, followed by a second distribution four weeks later, at the end of May. In two control zones, a classical single bait distribution was organised during the same periods as for the second distribution in the respective test zones. No statistical differences were observed for adult foxes or fox cubs sampled in the test and control zones neither for baits uptake nor for seroconversion rate. However, seroconversion rates observed in fox cubs population were significantly higher (P < 0.01) in areas vaccinated at the end of May (43 and 56%) compared with those vaccinated at mid-May (24 and 20%). The vaccinal efficacy of baits was also significantly (P < 0.05) increased for the fox cubs in the areas vaccinated at the end of May (46 and 57%) compared with those vaccinated at mid-May (24 and 25%). This increase in immunological response by fox cubs when vaccinating in late spring must be related to their development. In the early spring, fox cubs are generally too young to have access to baits or to be vaccinated when eating them. For most of these fox cubs, a second distribution will not constitute a booster. Therefore, in order to increase the efficient access of fox cubs to vaccine baits, Spring distribution of baits should preferably be organised during May or June rather than in April.

The protective effect of the lyophilised SAG2 oral vaccine bait DBL2, already demonstrated on laboratory dogs, needed to be verified on common Tunisian dogs. Seven Tunisian dogs consumed totally or partially one DBL2 bait containing 10(8.3) TCID50 of the highly attenuated rabies vaccine strain, SAG2. Five of the seven vaccinated animals survived a challenge administered 33 days later with a Tunisian canine street rabies virus to which five of the six controls that were not vaccinated and had no specific antibodies succumbed. The partial or total consumption of a single DBL2 bait thus conferred a protective immune response similar to that observed in laboratory dogs to dogs of poor health status. The sero-antibody response was, however, weak: only two vaccinated dogs exhibited a significant neutralising antibody response after vaccination and before the challenge, and four after the challenge.

The Borna disease virus (BDV) causes a disease of the central nervous system (CNS) in several vertebrate species. The progress made over the last 30 years in molecular biology has allowed us to identify the unique characteristics of the virus, such as its persistence in the CNS and the way it is expressed. This has allowed scientists to classify this pathogenic agent in a new family of RNA viruses. BDV affects a very large spectrum of hosts and is responsible for a disease characterised by behavioural anomalies. The large range of intra- or inter-specific symptoms of this disease (from persistence of the virus without clinical symptoms to CNS destruction) make epidemiological studies very difficult. Different diagnostic tools have allowed the detection of this infectious agent in different species around the world (central Europe, USA, UK, Japan, Iran, etc.). The disease can be fatal for sheep and horses (its primary natural hosts) and can infect other species such as rats, cattle, dogs, cats or pigeons. In human beings, BDV could be responsible for certain psychiatric disorders. In France, the limited number of epidemiological studies that have been conducted up until now (in veterinary and medical fields) does not allow scientists to ascertain whether the disease is present in France or not. Due to the suspected large geographical distribution of this infectious agent, however, we could expect the presence of BDV in France.

The safety of the SAG2 rabies virus, a highly attenuated mutant of the SAD strain intended to vaccinate dogs by the oral route, was evaluated in local Tunisian dogs and in five other local species likely to consume vaccine baits. These species were the domestic cat (Felis catus), the jackal (Canis aureus), the jerboa (Jaculus orientalis), the merion (Meriones sp.) and the gerbil (Gerbillus campestris). The vaccine was administered orally to 21 dogs, 11 cats and eight jackals and orally or intramuscularly to 62 wild rodents of the above-mentioned species. Seven dogs, one cat, five jackals all juvenile and with poor health status) and two rodents died for intercurrent causes. The others were observed for 60-180 days. No animal showed any rabies symptom. Seroneutralizing antibodies were observed in all experimental groups, only after vaccination, with the highest rate being observed in jackals and rodents. The rabies virus was detected in the oral cavity of three cats 6 h after oral instillation, but was not isolated later either in saliva or in salivary glands. Tissue samples (brain and salivary glands) from dead or euthanized animals were examined for the rabies virus antigen by a fluorescent antibody test. No rabies antigen was detected. These trials confirm the safety of the SAG2 strain on the Tunisian species already demonstrated by other authors on many other target and non target species.