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Biomedical subjects

G van Steenis

Publications and source records attributed to G van Steenis.

At least 37 records · Page 2Linked to original sources

Isolation and characterization of a papovavirus from cynomolgus macaque kidney cells.

A papovavirus was isolated from uninoculated kidney cell cultures of the Cynomolgus Macaque (Macaca fascicularis), in which it produced extensive cytopathologic changes after prolonged periods of culturing. On basis of virion morphology, genome size, and restriction endonuclease data, this virus was identified as a new isolate of the Stump-Tailed Macaque Virus (STMV) and subsequently named CK-strain (Cynomolgus kidney) of STMV. Without inducing c.p.e. the virus replicated also in BSC-1, VERO, human embryonic, and calf kidney cells. The relationship between STMV and SV40 was investigated by cross-blot hybridization between DNA fragments of both viruses. The region containing the SV40 regulating sequences showed strong homology with STMV DNA. No antigenic relationship between STMV and SV40 could be demonstrated. Antibodies to STMV were not found in sera from 20 Cynomolgus Macaques, but were detected in 25 out of 57 cattle sera and 6 out of 26 bovine colostrum samples. The serologic findings indicate that STMV is not a latent simian virus, but a virus of bovine origin.

Animals↗

The evaluation of a physical method for the quantification of inactivated poliovirus particles and its relationship to D-antigenicity and potency testing in rats.

The use of a density gradient procedure for the quantification of intact, inactivated poliovirus particles in vaccine preparations is described. The procedure is both sensitive and highly reproducible and the results correlate with those of potency tests in rats and with D-antigen content as measured by ELISA. Because of the occasional ambiguity observed with D-antigen assays, it is suggested that the density gradient procedure will provide valuable additional information for the in vitro assessment of inactivated poliovirus preparations.

Animals↗

A modified ELISA technique for the titration of antibodies to polio virus as an alternative to a virus neutralization test.

An ELISA based on inhibition of antibody binding for the determination of antibodies to polio virus type I is described. F(ab1)2-fragments of bovine antibodies to polio virus type I are used as the capture antibody thus lowering the background staining. A good correlation was found between the poliovirus neutralizing antibody level and the antibody titers as determined by ELISA.

Animals↗

Coronavirus-like particles in laboratory rabbits with different syndromes in the Netherlands.

Virus-like particles were identified from the plasma of rabbits which developed pleural effusion disease after inoculation with different strains of Treponema pallidum. These particles were considered coronavirus-like on the basis of their size, morphology, and buoyant density. Clinical and pathological manifestations of pleural effusion disease, which is probably the same disease entity as rabbit cardiomyopathy, resembled those of feline infectious peritonitis which is caused by another probable member of the Coronaviridae family. Coronavirus-like particles also were demonstrated in the feces of rabbits which had been inoculated with a 450-nm fecal filtrate of rabbits which died from infectious intestinal disease.

Animals↗

Antigen content of inactivated poliovirus vaccine for use in a one- or two-dose regimen.

The immunologic response to inactivated poliovirus vaccine following one and two doses has been studied in infants in developing and developed countries using vaccine prepared at the Rijks Instituut voor de Volksgezondheit, The Netherlands. Virus was grown in microcarrier cultures of monkey kidney cells, purified, concentrated, and inactivated with formalin. The vaccines used contained different quantities of D-antigen units for each of the three types. The data reveal that both antibody and immunologic memory (booster-type responsiveness) were induced in virtually all individuals following a single dose of a sufficient quantity of antigen. Immunologic memory was readily revealed by the booster-type response following a second dose given six months after the first. The degree of booster-type response to a second dose is linked primarily to the quantity of antigen used for primary immunization, and secondarily to the quantity of antigen used for the booster dose. The data base is presented for formulating the antigen content of an inactivated poliovirus vaccine that can be relied upon to be protective after the first dose when given alone or when incorporated with combinations of other antigens (diphtheria-per tussis-tetanus) that may require two or more doses.

Antibody Formation↗

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↗

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↗

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↗

Mousepox in the Netherlands.

Two independent outbreaks of ectromelia in mice occurred in The Netherlands. In both cases, the causative virus was isolated and identified as ectromelia virus on the basis of serology, demonstration of antigen by indirect immunofluorescence, negative contrast electron microscopy, morphology of lesions on chorioallantoic membranes of embryonated chicken eggs, and cytopathogenicity for mouse cells. Inoculation of the virus into the dermis of rabbits demonstrated a low virulence for this species.

Animals↗

Virologic control of monkeys used for the production of poliomyelitis virus vaccine.

Wild-caught or captive-bred cynomolgus monkeys (Macaca fascicularis) used at the National Institute of Public Health for the production of inactivated poliomyelitis virus vaccine are extensively controlled for the presence of antiviral antibodies in their sera. With relatively simple methods of segregation and hygienic measures it seems possible to keep the animals free of infections with certain viruses including Herpesvirus simiae and foamy viruses, which is of obvious importance for Public Health and for vaccine production.

Animals↗

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↗

Immunity to diphtheria, pertussis, tetanus, and poliomyelitis in children with acute lymphocytic leukemia after cessation of chemotherapy.

Antibody titers to diphtheria, pertussis, tetanus, and poliomyelitis (types I to III) were measured in previously vaccinated children with acute lymphocytic leukemia in remission after cessation of therapy. The response to revaccination one year after therapy was stopped was also studied. The patients' antibody titers were compared with those of healthy children, matched for age and sex. Two groups of patients were studied: one group (group A, N = 30) was given two drugs (6-mercaptopurine, methotrexate); the other group (group B, N = 19) was given three drugs (6-mercaptopurine, methotrexate, and cyclophosphamide) for maintenance treatment. In general, the patients' antibody titers were lower than those of healthy children, but in most patients they were still at levels considered to be protective. No significant differences in antibody levels between the two patient groups were found. A spontaneous rise in antibody titers in the first year after termination of therapy was not observed. After revaccination the rise in antibody titers was correlated with preexisting antibody titers in the same way in patients as in healthy children, and the antibody titers in patients and in healthy control subjects were on roughly the same level.

Adolescent↗

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↗

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↗