Rabies

Human vaccines

The first course of rabies treatment was administered under the supervision of Louis Pasteur, more than a century ago. Since then, rabies vaccines have always been among the first to benefit from progress in production and control. As regards vaccines for human use, around 1955 there was a transition from vaccines prepared from animal nerve tissue to embryonated eggs and very soon afterwards, around 1960, to adaptation of rabies virus to cultures of human diploid cells. The development of this vaccine, which remains the reference vaccine in comparative studies of immunogenicity, took long years. It was first registered in France in 1974 and a little later in north America. The late 1970s and the 1980s saw the development of a plethora of vaccines prepared on various cellular substrates such as primary explant cells of hamster, dog or fetal calf kidney, fibroblasts of chicken embryo, or diploid cells from rhesus monkey fetal lung, and finally cells from continuous lines (Vero cells). The production of some of these vaccines was stopped at the end of the 1980s whilst others have been administered to millions of patients.

The three vaccine types reviewed below belong to the latter category. They represent most of the vaccines that are traded internationally today.

Vaccine for humans prepared in human diploid cells

An inactivated rabies vaccine for human use was first prepared in cell culture in 1964. In 1966 it was shown that the human diploid cell (HDC) strain WI-38 was a suitable substrate for the propagation of the Pitman-Moore (PM) strain of fixed rabies virus. The original procedure for the production of this vaccine was described in the third edition. Since 1967, research and development have been carried out on this vaccine at the Mérieux Institute. The vaccine was first licensed for use in France in 1974 and commercial production started in 1978.

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Purified Vero cell vaccine for humans

Chapter 25 (Laboratory techniques in rabies, 4th edition, 1996) described the rabies vaccine for human use prepared in human diploid cells. In spite of its safety and high immunogenicity, the relatively low titre of virus production by these cells constituted a limitation to the large-scale production of a comparatively cheap rabies vaccine of equal quality. The inactivated poliomyelitis vaccine was the first vaccine made using this cell substrate, and led to the revision of the requirements for the vaccine by the WHO Expert Committee on Biological Standardization.

The technique developed by van Wezel, consisting of the culture of cells on microcarriers, stimulated large-scale cultures of cells for human vaccine preparations. Following the production of the inactivated poliomyelitis vaccine in Vero cells, studies were carried out to develop a human rabies vaccine. The resulting vaccine, which required a purification step in order to remove the residual cellular DNA, is known as the purified Vero cell rabies vaccines (PVRV).

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Purified chick-embryo cell vaccine for humans

This vaccine is prepared in primary chick embryo cells derived from specific pathogen-free (SPF) eggs. It is a freeze-dried preparation consisting of purified and concentrated rabies virus antigen inactivated with B-propiolactone.

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International standard for rabies vaccine

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