Vaccinia-rabies Glycoprotein Recombinant Vaccine Research Articles

ORAL RABIES VACCINATION STRATEGIES TOWARD RACCOON (PROCYON LOTOR) RABIES ELIMINATION ON SUBURBAN LONG ISLAND, NEW YORK, USA.

Approximately 1.86 million baits containing a vaccinia-rabies glycoprotein recombinant vaccine were distributed with helicopters, vehicles, and bait stations during 2006-10. A bait density of 250 baits/km2 effectively controlled rabies cases in enzootic and preepizootic areas. However, a cluster of 11 rabid raccoons at the eastern edge of infection resulted in the initiation of semiannual, high-density (500 baits/km2) vaccination campaigns in approximately 20% of the oral rabies vaccination zone during July and September (2007-09). Bait success (i.e., chewed sachets or removed baits) at bait stations was negatively associated with station distances from water. Conversely, bait success improved with increasing distances from roads. Bait stations deployed significantly more baits in developed open space when compared to low- and medium- to high-intensity developed areas. However, a difference was not detected between developed open space and forest habitats. Rabies was confined to 86 raccoons within 317 km2 (10%) of a 3,133 km2 suburban landscape, with a disproportionate number of rabid raccoons (n=74) in developed areas, when compared to 10 cases in forest-wetland habitats. Two rabid raccoons did not fall within either general land-use classification. Rabies advanced 15.1 km eastward at a rate of 6.4 km/yr during a 28-mo interval (2004-06).

Progress towards Bait Station Integration into Oral Rabies Vaccination Programs in the United States: Field Trials in Massachusetts and Florida.

Bait stations for distribution of oral rabies vaccine baits are designed for rabies management in highly-developed areas where traditional distribution of oral rabies vaccine baits may be difficult. As part of national efforts to contain and eliminate the raccoon (Procyon lotor) variant of the rabies virus (raccoon rabies) in the eastern United States, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services program, distributed vaccine baits by bait stations experimentally and operationally in Massachusetts during 2006-present, and in Florida during 2009–2015. In Massachusetts, a rabies virus-neutralizing antibody (RVNA) response of 42.1% for raccoons captured in areas baited with high density bait stations during 2011–2015 was achieved, compared with 46.2% in areas baited by hand, suggesting the continuation of this as a strategy for the oral rabies vaccination (ORV) program there, and for similar locations. Non-target competition for vaccine baits is problematic, regardless of distribution method. In Massachusetts, bait station visitation rates for targeted raccoons and non-target opossums (Didelphis virginiana) were similar (1.18:1) during 2006–2009 (p > 0.05). Bait station modifications for reducing non-target uptake were tested, and in Massachusetts, reduced non-target bait access was achieved with two design alternatives (p < 0.001). However, no difference was noted between the control and these two alternative designs in Florida. Due to ongoing trials of new vaccines and baits, the bait station performance of an adenovirus rabies glycoprotein recombinant vaccine bait, ONRAB® bait (Artemis Technologies, Guelph, ON, Canada) and a vaccinia-rabies glycoprotein recombinant vaccine bait, RABORAL V-RG®bait (Merial Limited, Athens, GA, USA), was compared. While uptake of the ONRAB bait was greater in Massachusetts (p < 0.001) in this limited trial, both types performed equally well in Florida. Since bait station tampering or theft as well as potential human bait contacts has been problematic, performance of camouflaged versus unpainted white bait stations was analyzed in terms of internal temperatures and maintaining a stable bait storage environment. In Massachusetts, camouflaged bait station interiors did not reach higher average temperatures than plain white bait stations in partially- or fully-shaded locations, while in Florida, camouflaged bait stations were significantly warmer in light exposure categories (p < 0.05). As ORV operations expand into more heavily-urbanized areas, bait stations will be increasingly important for vaccine bait distribution, and continued refinements in the strategy will be key to that success.

National surveillance for human and pet contact with oral rabies vaccine baits, 2001–2009

To determine the rate and absolute number of human and pet exposures to oral rabies vaccine (ORV) bait containing liquid vaccinia rabies glycoprotein recombinant vaccine and to evaluate factors that might affect human contact with bait to modify the program and reduce human exposure to the vaccine. Retrospective analysis of surveillance data (2001 to 2009). Reports on human and pet contact with ORV baits in states with ORV surveillance programs. Data were collected from passive, multistate ORV surveillance systems in Alabama, Arizona, Florida, Georgia, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, North Carolina, Ohio, Pennsylvania, Tennessee, Texas, Vermont, Virginia, and West Virginia. Data collected included the nature of human or pet contact with bait and vaccine, the caller's knowledge of the ORV bait program, local human population density, and other relevant demographic data. All 18 states participated in the surveillance program for at least 1 year, for a combined 68 years of observation. One thousand four hundred thirty-six calls were reported, representing 3,076 found baits (6.89/100,000 baits dropped); 296 (20%) calls were related to human contact with ruptured bait, and 550 (38%) involved pet contact with the bait. Six adverse events in humans were reported, one of which required hospitalization. Fifty-nine adverse events in pets were noted, all of which were nonserious. Findings from surveillance activities have been used to improve baiting strategies and minimize human and pet contact with ORV baits. Overall, human and pet contact with ORV baits was infrequent. Surveillance has led to early identification of persons exposed to ORV and rapid intervention.

Genetic characterisation of attenuated SAD rabies virus strains used for oral vaccination of wildlife

The elimination of rabies from the red fox ( Vulpes vulpes) in Western Europe has been achieved by the oral rabies vaccination (ORV) of wildlife with a range of attenuated rabies virus strains. With the exception of the vaccinia rabies glycoprotein recombinant vaccine (VRG), all strains were originally derived from a common ancestor; the Street Alabama Dufferin (SAD) field strain. However, after more than 30 years of ORV it is still not possible to distinguish these vaccine strains and there is little information on the genetic basis for their attenuation. We therefore sequenced and compared the full-length genome of five commercially available SAD vaccine viruses (SAD B19, SAD P5/88, SAG2, SAD VA1 and SAD Bern) and four other SAD strains (the original SAD Bern, SAD VA1, ERA and SAD 1-3670 Wistar). Nucleotide sequencing allowed identifying each vaccine strain unambiguously. Phylogenetic analysis revealed that the majority of the currently used commercial attenuated rabies virus vaccines appear to be derived from SAD B19 rather than from SAD Bern. One commercially available vaccine virus did not contain the SAD strain mentioned in the product information of the producer. Two SAD vaccine strains appeared to consist of mixed genomic sequences. Furthermore, in-del events targeting A-rich sequences (in positive strand) within the 3′ non-coding regions of M and G genes were observed in SAD-derivates developed in Europe. Our data also supports the idea of a possible recombination that had occurred during the derivation of the European branch of SAD viruses. If confirmed, this recombination event would be the first one reported among RABV vaccine strains.

Efficacy of rabies biologics against new lyssaviruses from Eurasia

New causative agents of rabies continue to emerge as shown by the recent description of four novel lyssaviruses from bats in Eurasia, Aravan (ARAV), Khujand (KHUV), Irkut (IRKV), and West Caucasian bat virus (WCBV). The effect of rabies vaccination prior to exposure to these new lyssaviruses was investigated in two animal models (i.e., Syrian hamsters and ferrets). The hamsters were vaccinated intramuscularly with a commercial human or veterinary vaccine or with an experimental vaccinia-rabies glycoprotein recombinant vaccine. At 5 weeks after vaccination, animals were challenged with ARAV, KHUV, IRKV, or WCBV, or with a traditional rabies virus of dog/coyote origin. Previously vaccinated and rabies-naïve ferrets were also challenged with the four new isolates. In addition, the combined effect of rabies immunoglobulin and vaccine after exposure to the four isolates was investigated in hamsters using commercially available human products or an experimental monoclonal antibody. Results showed reduced protection with pre-exposure vaccination and with conventional rabies post-exposure prophylaxis against all four new bat viruses. In general, protection was inversely related to the genetic distance between the new isolates and traditional rabies viruses. For example, the WCBV is the most divergent of these lyssaviruses, and neither pre-exposure vaccination nor conventional post-exposure prophylaxis provided significant protection. The potential impact of these new lyssaviruses on human and domestic animal health and the impact on the putative bat reservoir populations will require further field and laboratory investigation.

Contribution to rabies prevention

After the end of the Second World War, an outbreak of fox rabies invaded Europe. For the immunization of human populations and domestic animals against the risk of rabies transmitted by infected wild animals, it appeared necessary to replace the first generation of rabies vaccines (nerve tissue vaccines) by more potent and safer vaccines. The European vaccine manufacturers, in close collaboration with the research institutes engaged in rabies research, soon and quickly developed a second generation of rabies vaccines, produced in cell cultures including continuous cell lines grown in bioreactors of industrial scale. The third generation of rabies vaccines is already available: the vaccinia-rabies glycoprotein recombinant vaccine is presently applied on a large scale in some European countries for immunization of wildlife. The canarypox recombinant vaccine has already been considered and successfully tested for human immunization.

Rabies oral immunization.

My interest in oral immunization dates to 1950 when I fed a child the live, attenuated polio virus vaccine. During the ensuing several years, many more children were immunized with this vaccine, and these efforts culminated in mass oral immunization of 250,000 infants in the Belgian Congo, during the epidemic of true infantile paralysis. This immunization required six weeks to perform. Our current interest in oral immunization stems from the fact that our real problem, as far as rabies is concerned, is not domestic animals, and not even vaccines for humans, but for effective vaccines for wildlife. The experience, particularly of Europeans with foxes, has indicated that the eradication of rabies in wildlife cannot be achieved by reducing the reservoir species by killing, gassing, or any other rather barbaric method. Instead, immunization of the wild reservoir animals offers an alternative approach (Steck et al. 1982). The questions are, how and what type of vaccine could be used, and how effective it would be — and this is the subject of my contribution. I will be discussing only one type of vaccine — the vaccinia-rabies glycoprotein recombinant vaccine (V-RG). I do not need to present details about the vaccine, other than that it is obtained by the cDNA derived from the mRNA for rabies glycoprotein incorporated into a construct plasmid from which it is in turn incorporated with vaccinia virus TK gene plasmid (Kieny et al. 1984). Transfection of vaccinia-infected cells with the plasmid allows double reciprocal recombination in vivo and final construction of the V-RG recombinant virus vaccine with the rabies glycoprotein gene interrupting the vaccinia TK gene sequence.KeywordsRabies VirusOral ImmunizationOral VaccinationSubmandibular Lymph NodeRabies Virus GlycoproteinThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Glimpses into the future of rabies research.

Much is now known about the chemical composition of the rabies virus but little is known of its pathogenesis. Techniques used commonly in molecular biology research can and should be applied to questions about the behavior of the rabies virus and the responses of the challenged host so that new generations of vaccines may be produced. The vaccinia-rabies glycoprotein recombinant vaccine acts by inducing neutralizing antibody to rabies virus and completely protects various species of vaccinated animals against challenge with rabies virus. The vaccinia-rabies glycoprotein recombinant vaccine is the most promising of the new generation of rabies serums.