Recombinant vaccines for oral immunization of wildlife

The development of recombinant DNA technology has initiated a new era in rabies control. Recombinant vaccines cannot exhibit residual pathogenicity caused by rabies because they contain only single non-virulent gene products. The majority of the safety requirements for modified live-virus vaccines are also applicable to recombinant vaccines.

Various recombinant constructs (e.g. animal poxviruses or human or canine adenovirus as vector) expressing the rabies glycoprotein were tested in different target and non-target wildlife species by the oral route. The only recombinant that is now produced and used in large quantities is a vaccinia based recombinant product expressing the rabies glycoprotein (VRG).

VRG shares many basic properties with parental vaccinia virus (Copenhagen strain) but differs in other ways which make the vector virus safer. The deletion of the thymidine kinase gene dramatically decreases the pathogenicity of the vaccine for mice when it is given by the intracerebral and intraperitoneal routes. In addition, no viral spread from currently known ites of viral replication has been observed, and oral vaccination of dozens of animal species, including wild animals, has not revealed any residual pathogenicity.

When administered orally (by direct instillation in the mouth or in a bait) to young and adult foxes or raccoons, a dose of 10 8 TCID 50 (median tissue-culture infective dose) of VRG elicits high titres of virus-neutralizing antibodies and confers protection against a severe rabies challenge.

Studies have shown that the VRG vaccine is not pathogenic in over 10 avian and 35 mammalian species, including the majority of rabies reservoir hosts. Regardless of the vaccine dose or route of administration, the vaccinated animals have remained clinically normal, with no overt gross or histopathological lesions. Following oral administration, the VRG vaccine is cleared relatively quickly (e.g. within 48 hours). No abortifacient, teratogenic, or oncogenic side-effects have been noted. Large-scale field trials in foxes, raccoons and coyotes have been reported to date in Europe and North America.