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Rabies vaccines: a review of progress towards improved efficacy and safety.

Over the years, the technology for producing human rabies vaccines has undergone many improvements. These improvements consist in the use of tissue cultures for the production of viral antigens, replacing the former nervous tissue substrate vaccines. The low virus yields in tissue cultures led to the development of the concentration and purification of virus supernatants. Another technical improvement was obtained by using microcarriers for virus production in VERO cell suspension cultures. This technique permits commercial-scale production of rabies vaccine, lowering production costs and thus extending the availability of the vaccine to a broader population in developing countries. Besides improvements in rabies vaccine production technology, the use of various vaccination regimens and routes of administration in field trials has resulted in considerable gains in our experience of postexposure treatment (PET) of this disease. The standard WHO recommended regimen for PET using concentrated and purified tissue culture vaccines consists of a 5-dose course of intramuscular injections at days 0, 3, 7, 14 and 28. Reduced vaccination regimens such as the 2-1-1 have been proven to be efficient in raising protective antibody responses. Reduction in the total volume of rabies vaccine is also possible by using the intradermal route of injection, provided the vaccine is administered at several sites. The overall consequence is a progressive shift in the worldwide use of rabies vaccines from those of nervous tissue origin to the contemporary tissue culture vaccines.