Rabies Vaccines: The Third Generation

Rabies, a viral zoonosis is usually transmitted to humans through the bite of an infected animal. In many parts of the world, predominantly developing countries human rabies is still a disease of significant public health concern. Rabies also less frequently afflicts humans in the developed world, most cases occurring as the result of exposure to infected wild animals, especially rabid bats. Therapy administered following the onset of rabies symptoms is unsuccessful and the disease has a mortality rate of nearly 100% in humans. Post-exposure vaccination initiated shortly after exposure or prophylactic vaccination of humans considered to be at high risk to rabies virus exposure effectively controls or prevents infections. Current vaccines for human use are either based on brain derived or tissue culture grown inactivated rabies virus. Unfortunately, the former is inexpensive but associated with significant and often fatal side effects while the latter is safe but costly. The development of new, safe and affordable rabies vaccines is thus warranted. In recent years, researchers have developed second-generation recombinant viral and DNA vaccines for rabies. Overall, the DNA based rabies vaccines were found to be immunogenic in mice. However, the efficacy of these vaccines in larger species such as non-human primates was disappointing. Recombinant viral vaccines based on vaccinia or adenoviral vectors have demonstrated good efficacy in pre-exposure vaccination of rodents and of larger mammals, not withstanding they remain to be tested in post-exposure models.