[Post-vaccination measles immunity in children on long-term anticonvulsant therapy]. / Postvakcinalni imunitet za ospice u djece na dugotrajnoj antiepileptickoj terapiji.

In the prospective study, seroconversion and duration of immunity were examined by studying children on the longterm anticonvulsant treatment 5 years after application of monovaccine against the Edmonston-Zagreb measles. The patient group was composed of 35 children with epilepsy and the control group consisted of 65 children without epilepsy. Average age was 7.5 years for both groups. The examinees were mainly treated with monotherapy, most usually with phenobarbitone, carbamazepine and valproate. Good control of seizures was achieved in all children. Seroconversion was tested 6 weeks following vaccination in all examined children. The levels of titres of hemagglutination inhibiting (HI) antibodies did not differ significantly between examined children and controls (chi 2 = 2.588 p > 0.05). Nor did the correlation exist between the length of antiepileptic drug administration and the level of antibody titres (chi 2 = 0.75 p < 0.05). Five years after the vaccination, the level of titres of HI antibodies in epileptic patients and controls showed no statistically significant difference (chi 2 = 2.42 p < 0.05). There was also no correlation between the duration of receiving anticonvulsants and duration of immunity (chi 2 = 0.25 p < 0.05). The children with good control of seizures can be revaccinated, as well as the healthy children, 5 years after the primary vaccination.

Determination of foetal calf serum in vaccine preparations by immunoradiometric assay and enzyme-linked immunosorbent assay.

A simple and sensitive immunoradiometric assay (IRMA) for detection of foetal calf serum proteins in vaccine preparations has been developed. In this two-site sandwich assay the same preparation of polyclonal anti-FCS immunoglobulin (IgG) was used for coating the solid phase (as a capture antibody) and in a labelled form (I-125 labelled) for detection. The developed assay allows precise and accurate quantification of FCS proteins (down to 10 ng/ml) in vaccine preparations and has been used for screening of FCS residues (a) during production of measles vaccine, and (b) in various different commercial vaccine preparations. An enzyme-linked immunosorbent assay (ELISA) was also developed based on the same assay two-site sandwich principle, where anti-FCS was directly labelled with horse-radish peroxidase. ELISA was comparable in sensitivity and accuracy with IRMA.

Persistence of immunity against measles in persons immunized with Edmonston-Zagreb vaccine.

Cohorts of 30 children--470 in all--vaccinated against measles 2 to 17 years earlier were tested for measles heminhibiting antibodies. The vaccinees were randomly selected from a semi-urban, semi-rural population where the circulation of the wild measles virus has never been interrupted. The vaccinal status of the vaccinees varied widely, some were vaccinated only once, some twice or even three times, in some the primary vaccination was performed with a measles monovalent and in some with a combined MMR vaccine, only the revaccination having always been performed with a monovalent vaccine. The results of this serologic study reveal that the vaccine-induced immunity against measles does not fade with time, on the contrary, as judged by the mean geometric antibody titers, it rises. This is speculatively attributed to the booster effect of natural reinfection(s). Thereafter it is demonstrated that revaccination(s) do not yield a better immunity than the primary vaccination alone. This "revaccination", if withheld, helps only to attain a better coverage of children that have escaped primary vaccination.

[Detection of IgG and IgM antibodies to herpes simplex virus type 1 and type 2 in human serum using an immunoenzyme method (ELISA) and the complement fixation reaction]. / Detekcija IgG i IgM antitijela za herpes simplex virus tip 1 i tip 2 u ljudskim serumima pomocu imunoenzimne metode (ELISA) i RVK.

On the basis of borderline optical density values (OD) in an enzyme-linked immunosorbent assay (ELISA) resulting from comparative testing of this method with complement fixation reactions (CF), determination was made of a set criteria for negative, weakly positive and positive results of IgG and IgM antibody detection of Herpes simplex type 1 (HSV 1), respectively type 2 (HSV 2). Of the 192 examined specimens by ELISA, 69.2% and 49.5% IgG HSV 1 and HSV 2 antibodies were found respectively. The number of sera containing IgM HSV 1 od HSV 2 antibodies was low (5.7%), since in the majority of cases the relapsing form of infection was involved. The sensitivity of ELISA to IgG in comparison with CF was slightly higher with the HSV 1 antigen (69.2:68.2%), and apparently lower with HSV 2 (49.5:28.2%). ELISA permits partial differentiation to be made between HSV 1 and HSV 2 antibodies due to a greater degree of antigen purity compared with the unpurified antigen used in CF. In fact, CF is known not to possess the sensitivity necessary to differentiate between HSV 1 and HSV 2 antibodies. For diagnostic purposes, ELISA findings could be more appropriately expressed quantitatively, in corresponding measurement units.

[The development and duration of immunity in children vaccinated against measles with the Edmonston-Zagreb vaccine]. / Stvaranje i trajanje imunosti u djece cijepljene protiv ospica vakcinom Edmonston-Zagreb.

After routine measles-rubella-mumps (MRM) vaccine, seroconversion rate for measles heminhibiting (HI) antibodies in a group of 161 children was determined. Of the 154 children who had no HI antibodies in the first serum sample, 153 (99.3%) developed these antibodies in titres greater than or equal to 1:4 and 148 (96.1%) in titres greater than or equal to 1:8 at 6 weeks postvaccination. These results are in concord with the WHO standards. Another study was designed to evaluate persistence of HI antibodies to measles in a group of 123 children who were given MRM vaccine 1-6 years earlier. No significant decrease in HI antibody titers was recorded. It is concluded that immunity acquired through vaccination with the Edmonston-Zagreb measles virus strain in children aged 12 months to 3 years is satisfactory and that it does not decrease at least up to 6 years following vaccination.

Mumps vaccine L-Zagreb, prepared in chick fibroblasts. I. Production and field trials.

Leningrad-L3 Mumps Vaccine virus has been further attenuated by adaptation and passage on SPF chick embryo fibroblast cell cultures. This new mumps strain has been designated L-Zagreb and has been used to prepare mumps vaccines which meet the WHO requirements. Observations during both the field trial period prior to registration and during the later use of the vaccine showed that the few reactions observed were mild and that seroconversion was obtained in 88-98% of vaccines. The morbidity of mumps in Croatia declined more than tenfold after the introduction of the new vaccine. During a mumps epidemic, vaccine efficiency was calculated to be 97-100%.

Comparative study of two human diploid rabies vaccines administered with antirabies globulin.

The association of human rabies immune globulin (HRIG) to the vaccine is recommended for postexposure rabies treatment in cases of severe exposure. In a previous study using an abbreviated postexposure vaccination schedule it was observed that passive immunization could partially inhibit the active immune response, with three cell-culture purified vaccines but not with the concentrated human diploid cell vaccine (HDCV). In order to see if this difference was related to the purification process, the present study was designed comparing two HDCV, one concentrated and the other concentrated and purified, both of them administered in association with HRIG. The neutralizing antibody response in the vaccines was found to be identical with both vaccines, ruling out the role of the purification and confirming the excellent immunogenicity of both human diploid cell vaccines and the absence of inhibition of the active immune response by the association of HRIG to HDCV.

Interaction of rabies vaccine with human rabies immunoglobulin and reliability of a 2-1-1 schedule application for postexposure treatment.

Five commercially available rabies vaccines (HDCV, FBKC vaccine, PCEC vaccine, PVRV and PDEV) applied alone or combined with human rabies immunoglobulin (HRIG) were administered, by random allocation, to 161 volunteer vaccinees, using the abbreviated 2-1-1 postexposure immunization schedule. Protective levels of rabies antibody were demonstrated in all vaccinees by day 14, and in all but one vaccinee from day 21 to day 90. Partial inhibition of the antibody response due to HRIG was observed for three vaccines (PCEC vaccine, PVRV and PDEV). In terms of economy, reliability and rapid antibody induction, the 2-1-1 schedule proves superior to the presently recommended regimen for postexposure rabies prophylaxis.

An evaluation of second generation tissue culture rabies vaccines for use in man: a four-vaccine comparative immunogenicity study using a pre-exposure vaccination schedule and an abbreviated 2-1-1 postexposure schedule.

In a double-blind comparative trial the immunogenicity of three new tissue culture rabies vaccines was evaluated, using a commercial human diploid cell vaccine (HDCV) lot as the reference. Two different vaccination regimens, a pre-exposure schedule, and an abbreviated 2-1-1 postexposure schedule (two doses of the vaccine applied bilaterally on day 0, with subsequent single doses given on days 7 and 21) were employed. In both, two of the new vaccines, purified chick embryo cell vaccine and purified Vero rabies vaccine, induced an antibody response equivalent to that of HDCV, while the geometric mean titres for the fetal bovine kidney cell vaccine were somewhat lower. The 2-1-1 regimen, a candidate regimen for economical rabies postexposure treatment, evoked a rapid and high titre antibody response with all four vaccines, peaking on day 14.

Immune response to Edmonston-Zagreb measles virus strain in monovalent and combined MMR vaccine.

The live Edmonston-Zagreb measles vaccine is currently produced either on chick-embryo fibroblasts (CEF) or on human diploid cells (HDC). Its stability meets the WHO requirements. Since the vaccine licensure in 1967 the Edmonston-Zagreb measles virus strain has been administered to over 20 million vaccinees either as a monovalent vaccine or as a component of the combined MR, MMR and MM vaccines. Immunogenicity studies have shown the persistence of the elicited HI antibody for a minimum of 16 years. In children aged 13-17 months a greater than 95% seroconversion was recorded after subcutaneous administration both CEF and HDC vaccines. The vaccine has also been shown to be highly immunogenic when administered intranasally. In 6-12 month old infants the Edmonston-Zagreb monovalent vaccine elicited a 100% HI antibody response after both s.c. and i.n. administration. The GMT of antibody 42 days after vaccination was significantly higher in those given HDC vaccine, regardless of the age of the vaccinees or the route of immunization.

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.