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.

Figure 1

Construction of the vaccinia–rabies glycoprotein recombinant vaccine (V-RG). The SAD (Street Alabama Dufferin; Wandeler, 1991) rabies virus strain (a) was isolated from the salivary glands of a rabid dog in Alabama (USA) during 1935 and was attenuated to the ERA (Evelyn Rokitnicki Abelseth, 1964 [23]) rabies virus strain by repeated cell culture passages (b). The complementary DNA corresponding to the gene coding for the 524 amino acid G protein of rabies virus strain ERA was inserted into the double-stranded DNA genome of the vaccinia virus strain Copenhagen, under the control of (c) the 7.5 kDa vaccinia virus protein promoter [143], in the gene coding for thymidine kinase (TK). Shown is the TK region of the vaccinia virus genome with the inserted rabies virus G-cDNA from HindIII-digested plasmid pTG187-PRO.

Figure 2

Fishmeal polymer and coated sachet bait formats. The fishmeal polymer (FMP) bait (A) is a cube made of extruded fishmeal and fish oil aggregated by use of a hydrophobic synthetic polymer (Bait Tek, Inc., Orange, TX). Wax is used to hold the vaccine-laden polyethylene sachet inside the bait. The coated sachet (B) is smaller and lighter than the FMP and consists of a vaccine-laden polyethylene sachet coated with wax, cod liver oil and fishmeal crumbles. Photo credit: Merial, Inc. stock photo image.

Figure 3

Rabies prevalence in terrestrial animals and V-RG bait distribution volume, France—1984 to 2006. Wildlife ORV efforts began during 1986 using an attenuated rabies virus vaccine (SAD-B19) and continued from 1990 through 2005 using a combination of RABORAL V-RG and attenuated rabies virus vaccines (SAG1 and SAG2) (Data sources: [47, 101, 107, 150]).

Figure 4

Rabies prevalence in terrestrial animals and V-RG bait distribution volume, Belgium—1987 to 2003. Wildlife ORV efforts began during 1989 using an attenuated rabies virus vaccine (SAD-B19) and continued from 1990 through 2005 using aerial and ground distribution of RABORAL V-RG (Data sources: [47, 101, 107, 150] and personal communication, B. Brochier).

Figure 5

Rabies prevalence in terrestrial animals and V-RG bait distribution volume, Luxemburg—1987 to 2002. Wildlife ORV efforts began during 1988 using an attenuated rabies virus vaccine (SAD-B19) and continued from 1992 through 2002 using aerial and ground distribution of Raboral V-RG (Data sources: [47, 101, 107, 150] and personal communication B. Brochier).

Figure 6

Cases of domestic dog/coyote and gray fox rabies virus variants and V-RG bait distribution volume, Texas—1988 to 2014. Wildlife ORV efforts in Texas began in 1995 for coyote and 1996 for gray fox, both programs using RABORAL V-RG (Data source: modified from [128] with raw data provided by the Texas Department of State Health Services for production of graphics).

Figure 7

Rabies prevalence by species and V-RG distribution volume, Israel—1993 to 2014. Rabies prevalence in jackals, fox and other terrestrial species and V-RG bait distribution volume, in Israel—1993 to 2014 (Data source: personal communication B. Yakobson, Kimron Veterinary Institute, Israel).