Most of the rabies deaths in humans are due to dog bites. Mostly the dogs involved are stray- or community-owned dogs. An effective and an economical tool to combat this threat would be oral immunization of these dogs by a bait delivery system in addition to parental vaccination of reachable pets. Live oral Rabies vaccines have already been used for decades in Europe for foxes and in the USA for raccoons to control of wildlife rabies. However, the attenuated Rabies vaccine strains used world-wide are considered not safe enough under the Indian conditions
Our recent developments in improving the safety of live modified rabies virus are based on modifications of the original SAD strain. First a SAD mutant has been derived wherein the Arginine residue of Glycoprotein G at position 333 is replaced with aspartic acid (to obtain strain ORA-D). By the changing all three nucleotides of this Arginine amino acid at position 333 the change is now stable in mice and cell cultures passages. ORA-D is non-pathogenic for adult mice given intracerebrally (IC), but possesses residual pathogenicity for baby mice if given IC. Then a further deletion was introduced into the P-protein. This removes the LC8 binding site, thereby preventing axonal transport of the virion core along a neural tract. These steps lead to the development of a stable ORA-DP vaccine virus, which is able to multiply in cell culture as efficiently as the parent strain. ORA-DP now is even safe in 1–2 days-old suckling mice after intramuscular inoculation. The improved safety profile of ORA-DP helped in designing and developing a highly safe Rabies vaccine. Further to enhance immunogenicity of the vaccine, the ORA-DPC strain has been developed; in which the insertion is realized of an additional glycoprotein G derived from the CVS-strain (which included the replacement of Arg to Asp at 333). This not only to improve vaccine efficacy, but the additional G also in itself adds to improved safety. ORA-DPC is currently the best candidate Rabies vaccine strain available for oral immunization of dogs. Its enhanced immunogenicity induces higher neutralizing antibody titers and has greatly improved safety, even in immunosuppressed dogs.
