[Clinical trial of YU BHK Rabivak vaccine against rabies in volunteers]. / Klinicko ispitivanje YU BHK RABIVAK vakcine protiv besnila na dobrovoljcima.

The BHK (baby hamster kidney) continual cell line has been used for years in the production of rabies vaccine for animals. Becouse of the rich harvesting of rabies virus from this cell substrate, there is no need of the an additional virus concentration, so that the vaccine production can be organised in small local Pasteur Institutes as well. Although its long-range use in the veterinary medicine has proved that the BHK line is safe and that the vaccine is immunogenic, its use in the human medicine has been only recently studied. According to the latest recommendations of the Expert Committee for the Biological Standardisation of the WHO from 1998, residual cellular DNA in the vaccine is not a potential risk because the inactivation of the vaccine by the beta-propiolactone completely inactivates its possible biologic activity. In the work, the authors report the results of the third phase of the clinical trail of the YU BHK Rabivak vaccine on volunteers. The rabies vaccine studied, named YU BHK Rabivak, produced by Novi Sad Pasteur Institute, caused the generation of protective titre of virus-neutralising antibodies in all examinees: in 96.4% after 2 doses, in 99% after 3 doses, and in 100% after 4 and 5 doses of the vaccine. The registered side effects were expected, mild, did not need medical treatment, and were not more frequent than in the case of other vaccines from cell culture.

[10 years' of production and use of human rabies immunoglobulin in Yugoslavia]. / Deset godina proizvodnje i primene humanog imunoglobulina protiv besnila u Jugoslaviji.

Application of the rabies immunoglobuline is a compulsory part of the prophylaxis of rabies in all severe, transdermal lesions caused by rabies infected animals. Sylvatic rabies has spread in the past few years throughout the whole Yugoslavia, and human cases of rabies have also been reported in other East European countries. In order to achieve the highest level of rabies prophylaxis, apart from postinfective rabies vaccination, it is necessary to provide passive immunization using specific antibodies against rabies. After successful immunization of the young, healthy volunteers in 1990, National Blood Transfusion Institute, in cooperation with the Pasteur Institute from Novi Sad, prepared the first quantities of immunized plasma by plasmapheresis procedure and human rabies immunoglobuline. Without national production, sufficient quantities of human rabies immunoglobuline could not be provided, since the price on the world market is rather high (over $1000 per patient).

Immunogenicity of BHK-rabies vaccine in human volunteers.

The production of rabies vaccine on baby hamster kidney (BHK-21) cells for human use is discussed. Long term experience in application of this vaccine in animals, without any noticeable complications and findings of inactivation of contaminated DNA from the cell substrate by beta-propiolactone have justified its recommendation for human use. Preliminary results of applying this simple, adjuvant vaccine in volunteers, confirmed its good tolerability and immunogenicity.

[Economical production of rabies vaccine on cell cultures]. / Mogucnosti ekonomicne proizvodnje vakcine protiv besnila sa kulture celija.

By producing the rabies vaccine from cell culture, this vaccination has become safe, with minimal postvaccinal reactions. The first vaccine according to this technology was produced by Pavle (Paul) Fenje, former chief of department of the Pasteur Institute in Novi Sad. Many cell cultures have been introduced so far for the rabies virus multiplication: primary hamster kidney, fetal bovine kidney, chick embryo, continuous cell line monkey kidney (VERO), human diploid cell (HDC), etc. Some possibilities of an economical rabies vaccine production from a continuous BHK-21 cell line have been discussed and recommended.