[Preparation and use of inactivated vaccine against acute anterior poliomyelitis in the Netherlands].
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Biomedical subjects
Publications and source records attributed to G van Steenis.
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The preparation of inactivated polio and rabies vaccine in tissue culture has been developed into a "Unit Process" at our laboratory during recent years. The process comprises trypsinization of animal kidney cells by the perfusion method, cell/virus cultivation in microcarrier culture and concentration and purification of the virus suspension followed by inactivation. Also, the control tests on the virus suspensions and vaccines are performed, to the greatest possible extent, according to the same procedures. In the meantime, both vaccines thus prepared have been tested in man. High antibody titres have been obtained and no adverse reactions have been observed. The results of a field trial with inactivated poliovaccine, administered at different concentrations, will be presented by Dr Salk. Preliminary concepts for further development of the production and control of these inactivated virus vaccines are discussed.
Eleven laboratories from eight countries and four continents took part in a collaborative study to evaluate experimental procedures to be used in selecting the new standard reference rabies vaccine prepared in human diploid cell cultures. The following procedures were used : (a) the NIH potency test in mice, (b) the antibody binding technique (by either mouse inoculation or the tissue culture method), (c) virus-neutralizing antibody levels in mice used for the NIH test, and (d) antibody induction in human volunteers treated with vaccine alone and in combination with human rabies gamma globulin. The four methods used for determination of rabies antibodies were mouse inoculation, rapid fluorescent focus inhibition, plaque reduction and complement fixation techniques. All results were expressed in International Units as compared to the standard WHO serum and vaccine preparations. In general, a close correlation was noted in results from different laboratories, and it was recommended that the future rabies standard vaccine should be evaluated by three testing procedures, the NIH test, the antibody-binding technique, and antibody levels in mice used for the NIH test.
Two candidate reference rabies vaccines were tested in a collaborative study involving seven laboratories. Using four different testing procedures it was determined that both vaccine preparations were highly potent and demonstrated satisfactory stability in the thermal degradation test.
To establish the antigen content of a killed poliovirus vaccine sufficiently potent to induce immunity with one or two doses and to establish a reference standard vaccine which has been tested under field conditions, a titration was carried out in infants to determine the amount of each of the three antigenic types of poliovirus vaccine required to induce seroconversion with a single dose. It has been observed that over a critical range of antigen concentration there is an essentially linear relationship between antibody response and quantity of antigen administered. More than 90 percent of the groups studied had detectable antibody after receiving single injections of 80, 8 and 64 D-antigen units of Types I, II and III, respectively. Four-fold less antigen for each of the three types was less effective. The implications of these findings for an efficient immunization procedure are discussed.
In this paper the large-scale production of a purified inactivated rabies vaccine in primary dog kidney cells cultivated in microcarrier culture is described. The potency in the NIH-test and the antigenicity of this vaccine in other animal experiments were comparable with the antigenicity of vaccine prepared in human diploid cells. The antibody response was greatly enhanced by the addition of AIPO4 as adjuvant. The results of an initial clinical trial are presented.
Changes suggestive of being caused by a virus have recently been observed in primary rabbit kidney cells. In their nature and development they resembled those of parvoviruses. The changes were found in cultures from rabbits from various sources within and outside The Netherlands. If the changes are caused by a viral agent, this agent is most probably of rabbit origin, as exogenous infection, for example through trypsin, could almost certainly be excluded. However, no virus has yet been isolated nor could particles be made visible by electron microscopy in affected cells. Hemagglutination could not be demonstrated nor could antibody in rabbits. The possible nature of these changes will be discussed.