The development of vaccines that prevent rabies has a long and distinguished
history, with the earliest preceding modern understanding of viruses and the
mechanisms of immune protection against disease. The correct application of
inactivated tissue culture-derived vaccines is highly effective at preventing the
development of rabies, and very few failures are recorded. Furthermore, oral
and parenteral vaccination is possible for wildlife, companion animals and
livestock, again using inactivated tissue culture-derived virus. However, rabies
remains endemic in many regions of the world and causes thousands of
human deaths annually. There also remain no means of prophylaxis for rabies
once the virus enters the central nervous system (CNS). One reason for this is
the poor immune response within the CNS to infection with rabies virus
(RABV). New approaches to vaccination using modified rabies viruses that
express components of the innate immune system are being applied to this
problem. Preliminary reports suggest that direct inoculation of such viruses
could trigger an effective anti-viral response and prevent a fatal outcome from
RABV infection.