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Biomedical subjects

A L van Wezel

Publications and source records attributed to A L van Wezel.

At least 37 records · Page 2Linked to original sources
PubMed1981

Monoclonal antibodies to polioviruses. Production of specific monoclonal antibodies to the Sabin vaccine strains.

Murine lymphocyte hybridomas which produce neutralizing or non-neutralizing monoclonal antibodies to different type 1, 2 or 3 poliovirus strains were isolated. The majority of these monoclonal antibodies reacted with antigenic determinants present on different poliovirus strains of the same type. However, hybridomas producing monoclonal antibodies specific for each of the three Sabin vaccine strains were also generated.

Animals↗
PubMed1981

Control on the absence of DEAE-polysaccharides in DEAE-sephadex purified poliovirus suspensions by pyrolysis mass spectrometry.

Poliovirus suspensions produced in microcarrier culture of primary monkey kidney cells and purified by column chromatography on DEAE-sephadex have been tested for the presence of DEAE-polysaccharides (in essence DEAE-dextran) by pyrolysis mass spectrometry. Semi-quantitative evaluation of the pyrolysis mass spectra indicates that the concentration of DEAE-dextran in the purified poliovirus concentrates is below 20 ppm i.e. the lower detection level of the method. As the final vaccines contain a 1:50 to 1:100 dilution of the tested virus suspension, the DEAE-polysaccharide concentration in the vaccine will be below 1 ppm at least. Pyrolysis mass spectrometry appeared to be a vary suitable method for control on the absence of this component.

Animals↗
PubMed1981

D-antigen determination in polio vaccine production: comparison of gel diffusion and ELISA methods.

Up to now gel diffusion is widely used for in vitro determination of polio D-antigen. This method has several disadvantages, its relatively low sensitivity being the main one. Generally samples have to be concentrated, which requires fairly large amounts of material and often results in some loss of antigen due to adsorption. Two ELISA methods have been developed for determination of polio D-antigen. These tests have a high sensitivity, approximately 1 DU/ml, and require very small amounts of sample and antisera. Using the indirect method only one HRPO conjugated antiserum is needed for quantitation of type 1, 2 and 3 D-antigen. Comparison of D-antigen values obtained by ELISA and gel diffusion for a number of vaccines revealed a good correlation between the different methods. The indirect ELISA method has also been applied successfully for D-antigen quantitation of A1PO4 adsorbed DT-and DPT-polio vaccines.

Animals↗
PubMed1981

Potency testing of killed polio vaccine in rats.

Various laboratory animal species were considered for testing the potency of killed poliovaccine. The rat appeared most suitable for obtaining quantitative information by measuring the titre of the antibody response. There was, in general, a good correlation between antibody response in rats and D-antigen titre. This relationship appeared less clear for heat-degraded or long-stored vaccines.

Animals↗
PubMed1981

Killed poliovaccine: an evaluation of safety testing.

Several important changes in the production process of killed poliovaccine have recently taken place or are taking place concerning cell substrate as well as production techniques. Some of the consequences of these changes for the safety testing of the vaccine will be briefly discussed. Data will be presented to show that tests in tissue culture are more sensitive than those in monkeys for the detection of residual live poliovirus in vaccine. It is concluded that there is no need for an additional test in monkeys when tests in tissue culture are carried out according to W.H.O. requirements.

Animals↗
PubMed1981

Epidemiological implications of the isolations and intratypic serodifferentiation of poliovirus strains in the Netherlands.

From the results of virus isolation and serological studies it can be concluded that poliovirus does not occur endemically in the Netherlands. On the other hand continual importation of poliovirus is demonstrated among children of foreign workers, refugees and adoptive children. A certain part of these imported poliovirus strains appear to be wild type as shown by intratypic serodifferentiation with monospecific antisera. These strains are a continuous danger to non-immunized persons lacking neutralizing antibodies. The intratypic serodifferentiation with monospecific antisera also appears to be applicable for the differentiation of wild poliovirus strains and may therefore be a useful tool in epidemiological studies.

Adolescent↗
PubMed1981

Present state and developments in the production of inactivated poliomyelitis vaccine.

A review is given on the present state and developments in the production of inactivated poliomyelitis vaccine. Various aspects of the production such as cell substrates, large scale culture techniques, seed viruses and processing of virus harvests are discussed in view of safety, potency and economics. As far as cell substrates are concerned subcultured monkey kidney cells from captive-bred monkeys or non-tumorigenic continuous cell lines both cultivated in microcarrier culture are at the moment considered to be the best cell substrates in substitution for primary monkey kidney cells. Although with the present seed viruses highly potent vaccines can be prepared attention should be paid to the antigenicity and stability of the seed viruses especially type 1 seed virus. For processing of virus harvests concentration by ultrafiltration followed by purification with column chromatography is giving very pure virus suspensions. The results regarding yields and economics on the processing of virus harvests may be improved by application of affinity chromatography on immobilized antibodies. Inactivation by formalin has proved to be a reliable and safe method for the inactivation of the concentrated and purified virus suspensions.

Animals↗
PubMed1981

Production and potential use of monoclonal antibodies against polio viruses.

Lymphocyte hybridomas secreting monoclonal antibodies against different strains of polio virus type 1, 2, or 3 have been produced. For this purpose Balb/C mice were immunized with purified and inactivated virus suspensions and their splenocytes were fused with P3X63Ag8 mouse myeloma cells. Screening for antibody production was performed in an enzyme-linked immunosorbent assay (ELISA). Antibodies were produced either in cell culture or in Balb/C mice by passaging the hybridomas as solid or ascitic tumors, after they had been cloned at least three times by limiting dilutions in microtiter plates. Specificities of a number of these monoclonal antibodies were determined in the ELISA and in a neutralization test using different polio virus subtypes. The results indicate that for epidemiological studies monoclonal antibodies may prove to be very useful tools. Also the use of monoclonal antibodies for vaccine production (affinity chromatography; characterization of viral substructures) and routine vaccine control purpose (antigen quantification; neutralization of vaccine virus) seems attractive. Two of the neutralizing monoclonal antibodies against polio virus type 1, showed a selective immunoprecipitation with VP1, which suggests that VP1 is an important polypeptide for the induction of neutralizing antibody in vivo.

Animals↗
PubMed1981

Detection and elimination of cellular nucleic acids in biologicals produced on continuous cell lines.

Experiments have been conducted to determine the extent to which currently available purification techniques can remove contaminating substrate cellular DNA from inactivated poliovirus vaccine produced on continuous cell lines rising highly [32P]-labeled, nick-translated cellular DNA added to poliovirus suspensions, we found that purification procedures were capable, in small-scale experiments, of reducing contaminating DNA by factors of 10(3) (DNAse treatment followed by gel filtration) and 10(3)-3X10(5) (ion exchange chromatography). Sequential application of these purification steps should reduce contaminating cellular DNA to acceptable levels. We also examined the potential usefulness of immobilized nucleic acid hybridization techniques for the routine direct testing of residual cellular nucleic acids in final production lots of inactivated poliovirus vaccine and other biologicals. A filter hybridization test, using [32P]-labeled, nick-translated cellular DNA as a probe, was capable of detecting 40 pg of homologous cellular DNA. Using probes of higher specific activity the assay should be sensitive enough for use in routine quality control.

Animals↗
PubMed1981

Use of the ATG-treated newborn rat for in vivo tumorigenicity testing of cell substrates.

The ATG-treated newborn rat proved to be a sensitive model for tumorigenicity testing of cell substrates. HeLa cells in this model formed progressively growing tumors that regularly metastasized. Other cell types, among them third passage normal monkey kidney cells and Vero cells, gave rise to small cell nodules at the site of inoculation. These nodules were non-progressive in growth and did not metastasize.

Animals↗
PubMed1981

Theoretical and practical considerations in the application of killed poliovirus vaccine for the control of paralytic poliomyelitis.

This paper contains a summary of the principles upon which the preparation and use of killed poliovirus vaccine (KPV) are based, as well as a summary of earlier and more recent work suggesting the feasibility of formulating a KPV preparation that would be fully and durably effective in a one- or two-dose regimen. The essential factor in the preparation of such a vaccine is the inclusion of a sufficient mass of the immunizing antigen, for each of the three antigenic types of poliovirus, to induce the formation of humoral antibody and/or immunologic memory after the first dose. The results of a series of studies carried out in West African and Scandinavian countries are summarized, which suggest that such a vaccine should contain 40, 8, and 32 D-antigen units for types I, II and III, respectively. If the D-antigen unit measurement is to be used as a guide to KPV standardization, the details of the method of manufacture are important; in this regard, the method of vaccine preparation used at the Rijks Instituut voor de Volksgezondheid should serve as a reference standard for the preparation of vaccines expected to produce the effects described.

Antibody Formation↗
PubMed1981

Breeding of Macaca fascicularis for poliovaccine production.

In our Institute Cynomolgus monkeys (M. fascicularis) are mainly used for production and control of poliovaccine. In 1974 a small individual breeding colony was started. Last year the colony was enlarged with 10 harem groups. Based on colony reproduction data, group breeding seems more successful than individual breeding. Owing to developments in the production of poliovaccine, a state of total self supply is within reach. However attention must be paid to factors reducing breeding results, comprising aggressive interactions and disturbed mother-care. Finally replacement of breeding stock might require rearing conditions which are not compatible with those necessary for the establishment of a Foamy virus and Herpes-B virus breeding colony.

Animals↗
PubMed1981

Quantitative determination of rabies antigen by ELISA.

Two ELISA methods are described for quantitation of rabies envelope glycoprotein in suspensions containing liver or inactivated virus. One of these methods is currently used for "in process" control at the production of inactivated rabies vaccine in our laboratory. The results obtained with the ELISA-test have been compared with those from the classical NIH-test for a number of freeze dried vaccine preparations. Although no perfect correlation was obtained good vaccine lots could easily be distinguished from poor ones. Using the ELISA-test already at the start of the production process predictions can be made on the quality of the final product. At such the ELISA-test may be considered as an improvement in the standardization of inactivated rabies vaccine production.

Animals↗
PubMed1980

The production of inactivated poliovaccine on serially cultivated kidney cells from captive-bred monkeys.

Serially cultivated kidney cells from captive-bred monkeys appear to be very suitable as cell substrate for the production of inactivated poliovaccine. Up to about the 12th generation level no differences in cell growth and virus yield were observed. Also from a safety point of view, application of such cells is preferable to primary cells from wild-caught monkeys, as no evidence was found for the presence of monkey viruses or oncogenic properties in these cells. Application of these cells for the production of inactivated poliovaccine will reduce the number of monkeys needed for this purpose about 50 times and, therefore, could contribute considerably to solve the problem of shortage of monkeys in the world.

Animals↗
PubMed1980

Direct enzyme linked immunosorbent assay (ELISA) for quantification of poliomyelitis virus D-antigen.

The proposed micro-ELISA assay by means of the double antibody method involves three steps: adsorption of type specific antiserum on micro-wells; simultaneous incubation of antigen and Horse Radish Peroxydase (HRPO) conjugated antiserum; substrate incubation followed by photometric measurement of absorbance at 403 nm. Preliminary results seem generally in good agreement with those obtained by other tests such as gel diffusion and indirect ELISA.

Antigens, Viral↗
PubMed1980

Concentration and purification of poliovirus by immune adsorption on immobilized antibodies.

Antibodies to poliovirus type 1, 2 and 3 have been coupled to Sepharose 4 B. The immune sorbentia have high binding capacities for both live and inactivated virus. Bound antigen is eluted with a high concentration of ammoniumisothiocyanate. Immediately after elution the chaotropic salt is removed by gelfiltration. The antigen recovery with inactivated virus was low; however, with live virus a good recovery was obtained. Therefore, immune adsorption seems to be applicable for concentration and purification of large amounts of live poliovirus.

Antibodies, Viral↗
PubMed1980

Use of captive-bred monkeys for vaccine production.

Cynomolgus monkeys (Macaca fasicularis) were bred in captivity for the production and control of inactivated poliomyelitis vaccine. Compared to imported wild-caught animals the captive-bred monkeys contracted fewer virus infections, as evidenced by results of serological examination, and yielded remarkably clean cell cultures. These cultures could be grown in series and appear very suitable for the production of viral vaccines.

Animals↗