Micrograph depicting histopathologic changes associated with rabies encephalitis Courtesy Centers for Disease Control and Prevention

Zoonotic potential and public safety concerns make it important to determine how to vaccinate to wildlife reservoir species (eg, striped skunks, raccoons, red foxes) against rabies virus while having minimal impact on the human population and nontarget wildlife. However, virus and host variations and residual pathogenicity in the environment have made this difficult. An oral rabies vaccine developed using a recombinant human adenovirus vector containing the ERA rabies virus glycoprotein gene has shown capability of eliciting immune response against rabies in laboratory and field settings. This study examined how this vaccine (ONRAB) persists within tissues and is shed via feces and saliva of target and nontarget animal species, thus exploring residual environmental risks to widespread distribution of the ONRAB baits for rabies control.

Oral and rectal swab samples were collected from 84 red foxes, 169 striped skunks, 116 raccoons, and 155 nontarget small mammals representing 10 species. The samples were tested for ONRAB DNA via real-time PCR. None of the samples analyzed exceeded the upper limit of ONRAB DNA previously applied to assess viral shedding. This study confirmed previous findings that viral replication and shedding following vaccination with ONRAB is likely short-lived and that, under normal circumstances, risk for transmission of ONRAB vaccine virus in the natural environment is minimal.

Rabies vaccine delivered in baits for the control of rabies in reservoir wildlife species is not new; there is a long history of its successful application in Europe and North America. Earlier programs have used either live attenuated rabies virus (which risks residual pathogenicity) or recombinant vaccinia virus expressing the rabies virus glycoprotein. Recombinant viral vectored vaccines are safer, as there is no reversion to virulence when only a single rabies virus antigen is expressed by the “carrier” virus.

Apart from the control of rabies in wildlife reservoirs, use of oral vaccines delivered in baits has potential application for rabies control in free-roaming populations of domestic dogs in developing countries. There are successful canine rabies control programs in African and Asian countries, where rabies remains a prevalent and significant disease, accounting for an estimated 20,000 human deaths in India alone—primarily children who are more likely to be bitten by rabid dogs. Rabies control programs generally rely on capture of free-roaming dogs, needle injection of killed adjuvanted vaccines, and sometimes neutering before release.

When at least 70% of a dog population can be vaccinated, excellent rabies control in dogs and humans can be achieved, and these bait programs are far more effective than culling free-roaming dogs. A useful adjunct to these programs would be the ability to vaccinate even more of the dog population via the use of oral vaccine delivered in baits. Concerns for children finding and ingesting baits has led to reluctance regarding this practice, but the improved safety of recombinant vaccines addresses some of these concerns.
The described approach provides an alternative vectored vaccine for oral delivery. Another approach has been to create a safer version of the traditional Street Alabama Dufferin (SAD)-attenuated rabies vaccine through a series of 3 genetic manipulations: engineering a mutation in the gene encoding the SAD rabies glycoprotein, deleting the gene encoding the P protein, and then enhancing immunogenicity by adding an additional glycoprotein from a different virus strain. This ORA-DPC vaccine is a candidate for incorporation into oral baits for rabies control in free-roaming dog populations. Such novel products will require regulatory approval but may significantly impact the global struggle for control of this devastating disease.—Michael J. Day, BSc, BVMS(Hons), PhD, DSc, DECVP, FASM, FRCPath, FRCVS

An assessment of ONRAB oral rabies vaccine persistence in free-ranging mammal populations in Ontario, Canada. Sobey KG, Walpole AA, Rosatte R, et al. VACCINE doi.org/10.1016/j.vaccine.2013.02.057.

This capsule is part of the WSAVA Global Edition of Clinician's Brief, and the One Health Initiative