The present status of rabies vaccine development and clinical experience with rabies vaccine.

Attempts to control human rabies have a long history: animal and human vaccines provide efficient weapons for prevention. In this presentation, we would like to consider the different rabies vaccines available for human use, and particularly the modern vaccines produced in cell culture. Rabies virus is considered as an unique virus, but in fact, 5 groups of rabies fixed strains are used throughout the world to produce human rabies vaccines: Pasteur, Beijing, Flury, Fuenzalida and SAD strains. The Pasteur-derived strains, designated PV or PM, are the most widely used for the production of traditional vaccines of the Semple or Suckling Mouse Brain (SMB) types, but also for the production of modern cell culture vaccines: Human Diploid and Purified Vero Cell vaccines (HDCV and PVRV). The different rabies vaccines should be classified according to the cell system used to cultivate the virus: animal systems are still employed to produce the old traditional vaccines-Semple and SMB-which continue to be produced in several countries; Primary cell systems, particularly Hamster Kidney and Chick embryo cells, are used; Cell lines are presently the most interesting approach for vaccine production. The use of the human diploid cell system permitted the development of the HDCV, the most widely distributed cell culture rabies vaccine, and today considered as the reference vaccine. The heteroploid VERO cell line was introduced in 1982 to the production of inactivated rabies vaccine; it retained all the advantages of the Human Diploid Cell system, while offering the possibility of the large scale industrial production of PVRV. For both HDCV and PVRV, production security is guaranteed by the existence of a master cell seed and working cell bank, with a complete history of the cell, a limited number of passages and permanent and total quality control of the cell substrate. The principal human rabies vaccines produced worldwide at present using cell culture are compared, in terms of their technical characteristics and their capacity economically to face worldwide vaccine needs. The greatest needs are today in tropical countries, where only a limited amount of modern cell culture vaccines are used.