Oral vaccination of wildlife using a vaccinia–rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG®): a global review

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-017-0459-9) contains supplementary material, which is available to authorized users.

Benefit-cost analysis of the policy of mandatory annual rabies vaccination of domestic dogs in rabies-free Japan

“…On top of these basic components of the economic burden, there would be additional costs incurred in containing a non-canine rabies outbreak, e.g. extra manpower would be needed to support immediate stray cat depopulation in face of an outbreak involving domestic cat, while oral rabies vaccination (ORV) might be implemented in the long term if a wildlife rabies outbreak became endemic in the country [30]. Overall, the current study provided a generic framework for future research to estimate the potential economic burden of different rabies incursions in Japan.…”

Mucosal vaccines and technology

“…Mucosal delivery of vaccines through baiting allows free-ranging animals to voluntarily uptake vaccines, in order to break down interspecies transmission of infectious disease between wild and domesticated animals. Arguably, the most successful bait vaccine is RABORAL V-RG ® which, following distribution into wildlife habitats, has aided eradication of wildlife rabies from Belgium, France and Luxembourg [27]. Wildlife bait vaccination has also helped to control other pathogens, including classical swine fever in wild boar (Sus scrofa) in Europe [28] and plague in prairie dogs (Cynomys spp.)…”

Replication-inducible vaccinia virus vectors with enhanced safety in vivo

“…and relatively low cost of production [57,58]. Successful examples include a recombinant VACV expressing the rabies virus glycoprotein (V-RG) that has been used in Europe and North America against sylvatic rabies [59], and a VACV expressing rinderpest virus glycoproteins provided long-term sterilizing immunity in cattle [60]. Currently, a number of clinical trials are underway for animal and human vaccines, immunotherapies, and oncolytic therapies based on replication-competent VACV vectors [61,62].…”