Purified chick embryo cell rabies vaccine: economical multisite intradermal regimen for post-exposure prophylaxis.

The standard six-dose intramuscular (i.m.) rabies post-exposure vaccine regimen using a new purified chick embryo cell (PCEC) vaccine was compared with two economical multisite intradermal (i.d.) PCEC regimens, a multisite i.m. PCEC schedule and a subcutaneous regimen using a suckling mouse brain (SMB) rabies vaccine manufactured in Thailand. The neutralizing antibody results for the four-site and eight-site i.d. and the standard i.m. PCEC regimens were similar over 3 months. A three-site i.m. PCEC regimen had no advantage. The SMB vaccine gave the lowest antibody levels. Human rabies immune globulin therapy significantly increased the GMT of all groups on day 7, unlike equine antirabies serum (EARS). Both antisera suppressed antibody responses to PCEC on days 14 and 28. Three generalized reactions probably related to EARS were the only serious side effects. An eight-site i.d. PCEC vaccine regimen proved as immunogenic as the routine i.m. schedule and, if implemented as post-exposure prophylaxis, would be the cheapest widely available tissue culture vaccine regimen. The protective efficiency should now be tested in patients bitten by rabid animals.

Pre-exposure studies with purified chick embryo cell culture rabies vaccine and human diploid cell vaccine: serological and clinical responses in man.

Clinical reactions and neutralizing antibody responses to six pre-exposure regimens of purified chick embryo cell culture rabies vaccine (PCECV) and human diploid cell strain rabies vaccine (HDCSV) were studied in 177 volunteers. Antibody kinetics, height of the response and persistence of antibody over two years were virtually identical after PCECV and HDCSV. An antibody response was detected in all subjects on day 14 when the highest titres were found after two intramuscular (i.m.) 1.0 ml doses of a schedule of immunization on days 0, 7 and 21. In comparison, a schedule of immunization on days 0, 28 and 56 ultimately evoked the highest titres 21 days after the final injection, but antibody persisted equally well over two years with either schedule. Neutralizing antibody titres were lower after intradermal (i.d.) vaccination with 0.1 ml compared to 1.0 ml i.m. on days 0, 7 and 21, but when given on days 0, 28 and 56 the responses were comparable. Three subjects with a personal or family history of atopy developed urticarial lesions after PCECV. Both vaccines were otherwise well tolerated.

Side effects of BCG vaccination with strain Copenhagen 1331.

In the Federal Republic of Germany a BCG vaccine of strain Copenhagen 1331 is used. This vaccine was delivered with a content of 100,000 to 200,000 viable units per dose. Even in this small range one can see a relationship between spontaneously reported side effects, especially suppurated lymphadenitis in newborns. The lower the dosage the rarer the side effects. A diminution of viable units to a concentration of 100,000 to only 150,000 per dose shows a better compatibility though the conversion rate is still greater than 90%. Relevant side effects in schoolchildren or adults were not registered.

Purified chick embryo cell (PCEC) rabies vaccine for human use: clinical trials.

The purpose of the study was the clinical evaluation of the new PCEC-Rabies-Vaccine. In 620 healthy volunteers mild local side-reactions could be observed in less than 2% of the vaccinations. No relevant general reactions have been reported or seen after the 2200 injections apart three cases of urticaria. All the 218 volunteers tested developed neutralising rabies antibodies of the IgG-type between day 0 and day 30 after the first vaccination dose. In 45 patients the PCEC-Rabies-Vaccine, applied together with human rabies immunoglobulin in a postexposure vaccination, afforded protection against rabies after contact with a proven rabid animal. The clinical trials are proof that the compatibility and efficacy of the PCEC-Rabies-Vaccine match the high standards established by the HDC-Rabies-Vaccine.

Clinical trials in healthy volunteers with the new purified chick embryo cell rabies vaccine for man.

Behringwerke has developed the new, safe and economical purified chick embryo cell (PCEC) rabies vaccine. Due to the purification by zonal centrifugation the compatibility of this vaccine is excellent. Among 933 vaccinations in 219 healthy volunteers the only side-effect was mild pain at the injection-site in 17 vaccinations (1.7 per cent). The sero-conversion of PCEC rabies vaccine was 100 per cent in the tested healthy volunteers. The kinetics of antibody induction after PCEC rabies vaccine is comparable to antibody induction after HDC rabies vaccine. PCEC rabies vaccine induces cellular immunity as measured in lymphocyte transformation test, but no interferon activity.

A new inactivated tissue culture rabies vaccine for use in man. Evaluation of PCEC-vaccine by laboratory tests.

A new inactivated rabies vaccine (purified chick embryo cell vaccine) has been developed using the Flury LEP-C 25 strain of rabies virus propagated in primary chick embryo cell cultures. The antigen was purified and concentrated by continuous density gradient centrifugation and inactivated by betapropiolactone. This vaccine was tested for innocuity, tolerability and protective capacity in a series of laboratory tests and compared with human diploid cell strain (HDC)-vaccines of similar antigenicity. The results indicated that this new vaccine was excellently tolerated and that its protective activity met the high standard of HDC-vaccine, conditions which were imposed on this vaccine before entering clinical trials in man.

Morphological and electrophysiological aspects of dissociated cultures of rat CNS.

Rat central nervous system has been cultured up to 6 weeks after complete dissociation. Maturation of different cell types has been followed in the quasi monolayer by phase contrast microscopy. Dorsal root ganglion (DRG) neurones usually differed from central nervous system (CNS) neurones by their spherical shape accompanied by only one or two processes, exact identification of cell types, however, was usually only possible by combining morphology with electrophysiology. Scanning electron-microscopy revealed a more extensive arborization of neurites and a higher number of presumed synaptic structures in cultures after 2 weeks of culturing. Layers of ependymal cells were also found. The different cell types were further identified by determining their membrane properties. Glial cells had higher resting membrane potentials (-56 +/- 9.7 mV) than CNS neurones (-49 +/- 10.2 mV), while the membrane potential of DRG neurones lay in-between the two (-53 +/- 1.7 mV). The sequence for input resistance was: DRG neurones (30 +/- 9.3 M omega) greater than CNS neurones (18 +/- 10.5 M omega) greater than glial cells (9.3 +/- 5.2 M omega). In CNS neurones the input resistance is correlated with the membrane potential, which is not the case for glial cells. Action potentials of DRG neurones exhibited delayed repolarisation increasing the spike duration to three times that of CNS neurones.

[Immunization against tetanus - studies about the duration of protection (author's transl)]. / Betrachtungen über die Dauer des Tetanusimpfschutzes.

In spite of proper treatment tetanus carries a high mortality up to 75% and more Since 1927 an active immunization against tetanus is available; it prevents the disease. With a radioimmuno-assay antibodies in the blood, which are neutralizing the tetanus toxin, can be estimated accurately. In 92 healthy persons below 55 years, who had been vaccinated between two up to ten years previously, antibody titers sufficient to prevent the disease were found without any exemption. The increase of antibody-titers after active immunization in healthy persons is described; it depends on the basic titer. If in case of a preexisting high level of neutralizing antibodies an active immunization is performed, allergic reactions of Arthus- or tuberculine-type may occur.

Normal and pseudorabies virus infected primary nerve cell cultures in scanning electron microscopy.

Primary cell cultures from the central nervous system of the embryonic rat were inoculated with pseudorabies virus. Their morphological changes were studied by phase contrast microscopy and by scanning as well as by transmission electron microscopy. Uninfected cultures display two distinct cell layers in scanning electron microscopy: a flat continuous monolayer supports a heterogeneous population of individual, presumably neural cells, which emit processes of different number and size. The latter cells form contacts by a dense network of fibres. Infectious virus is propagated in these nerve cell cultures with similar effectivity as in other cultures. The infectoin leads to fusion and death of the cells. By the time the cytopathic effect is visible, nearly all cells, including those of neuronal and those of nonneuronal appearance, are studded with ample amounts of virus-sized particles. The particles represent viruses as demonstrated by transmission electron microscopy or by treatment with a hyperimmune serum directed against pseudorabies virus structural components. Hyperimmune serum leads to clustering of the particles at the cell surface. The amount of virus particles per surface unit was about 10 times higher on neural cells as compared to primary rabbit kidney cells. The concentration of infectious particles in the supernatant, however was approximately the same. The system described appears to be useful for the study of acute virus effects on neural tissue under strictly controlled conditions.