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Biomedical subjects

S A Plotkin

Publications and source records attributed to S A Plotkin.

At least 163 records · Page 9Linked to original sources
PubMed1984

Varicella vaccine trials in healthy children. A summary of comparative and follow-up studies.

Beginning in 1979, OKA and KMcC strains of varicella zoster virus (VZV) vaccine were administered to 369 healthy seronegative children in a sequence of ten comparative clinical trials. Postimmunization clinical reactivity was minimal with the OKA vaccines but was unacceptably high (32%) with the KMcC passage-40 vaccine. Ninety-three percent to 100% immunogenicity was noted by fluorescent antibody assay and in vitro lymphocyte proliferation to VZV antigens. Follow-up studies demonstrated persistence of antibody and in vitro lymphocyte proliferation responses and protection or modification of infection nine to 48 months after immunization. Only five episodes of mild varicella occurred in children in whom seroconversion had occurred. These episodes were noted after at least 281 known varicella exposures. Vaccine virus reactivation as zoster had not occurred in any child.

Adolescent↗
PubMed1984

Intranasal administration of RA 27/3 rubella virus vaccine. A clinical trial in young adults.

Of the vaccines and inoculation routes studied for the prevention of rubella, only the RA27/3 vaccine, administered intranasally, has the ability to stimulate a humoral antibody pattern very similar to that evoked by wild rubella infection. Because information about intranasal (IN) vaccination has only been obtained using the RA 27/3 vaccine manufactured in Europe, we conducted a trial of IN vaccination among young adults using Meruvax II which is manufactured in the USA. Of 597 family planning clinic patients screened in 1980-1981, 71 (11.9%) were susceptible to rubella; forty-one subjects were randomly assigned to receive IN or subcutaneous (SC) vaccine. All 20 SC vaccinees, but only 8/21 (38%) IN vaccinees, were successfully immunized. We conclude that standard doses of commercially available RA 27/3 vaccine are insufficient for IN immunization against rubella. Additional study of the dose-response relationship is needed if IN vaccination is to be recommended.

Administration, Intranasal↗
PubMed1984

Natural killing of cytomegalovirus-infected targets in renal transplant recipients.

The ability of peripheral blood mononuclear cells of renal transplant recipients to lyse cytomegalovirus (CMV) infected fibroblasts was determined in an 18-hr 51Cr release assay. Natural killing (NK) against CMV-infected targets was generally depressed for the first two years after transplantation. In three individuals who developed CMV disease after transplantation, NK activity against CMV-infected and uninfected targets rose to high levels following reductions in immunosuppressive therapy and in temporal association with resolution of disease.

Adult↗
PubMed1984

Cells infected with human cytomegalovirus release a factor(s) that stimulates cell DNA synthesis.

Culture supernatants of permissive and non-permissive cells infected with human cytomegalovirus (HCMV) contain a growth factor that enhances the DNA synthesis and mitotic activity of target cells. This cytomegalovirus growth factor CMV-GF) is a heat-stable, acid-labile polypeptide that is sensitive to trypsin and dithiothreitol. CMV-GF is an early product of the infected cells and defective virions are primarily responsible for its induction. Microtubule depolymerization is necessary for the induction of DNA synthesis by the CMV-GF, since taxol, an inhibitor of microtubule depolymerization, blocks its effect.

Alkaloids↗
PubMed1984

Susceptibility of vaccine strains of varicella-zoster virus to antiviral compounds.

Using a plaque reduction assay, we determined the 50% effective doses of six antiviral compounds against low- and high-passage viruses of the KMcC and Oka strains of varicella-zoster virus vaccine. The potency, as indicated by the ranges of 50% effective doses (micrograms per milliliter) of the antiviral compounds, in decreasing order was as follows: (E)-5-(2-bromovinyl)-2'-deoxyuridine, 0.0007 to 0.0035; 1-(2'-flouro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine, 0.0063 to 0.0091; aphidicolin, 0.092 to 0.180; acyclovir, 0.79 to 1.81; vidarabine, 0.62 to 2.10; and phosphonoformic acid, 8.18 to 16.4. Susceptibility to the various antiviral compounds was independent of passage level or strain. These data, along with the available in vivo data, indicate that varicella-zoster virus vaccine infections requiring antiviral therapy most probably would be treated as effectively as would natural varicella infections.

Antiviral Agents↗
PubMed1984

Rotavirus-specific antibodies in fetal bovine serum and commercial preparations of serum albumin.

Rotavirus-specific antibodies were detected in fetal bovine serum, bovine serum albumin, and human serum albumin by radioimmunoprecipitation with the NCDV strain of bovine rotavirus as the detecting antigen. Fetal bovine sera neutralized bovine rotavirus in a plaque reduction neutralization test to titers of 1:20 or greater. Immunoglobulins purified from fetal bovine serum by protein A-agarose affinity chromatography precipitated rotavirus antigens but did not neutralize bovine rotavirus. Rotavirus antibodies in fetal bovine serum and in purified serum albumin preparations may interfere with diagnostic assays for the detection of rotavirus antigens or antibodies.

Animals↗
PubMed1984

A murine model for oral infection with a primate rotavirus (simian SA11).

Simian rotavirus SA11 was shown to replicate in the gastrointestinal tracts of infant mice after oral inoculation. Clinical symptoms, histopathological changes in the small intestinal mucosa, and the type-specific humoral immune response were all characteristic of rotavirus-induced gastroenteritis. The availability of this small animal model for the study of a primate rotavirus infection should expedite analysis of the immune response necessary for protection against challenge.

Animals↗
PubMed1984

HCMV envelope antigens induce both humoral and cellular immunity in guinea pigs.

Antibody and cellular immunity were measured in guinea pigs immunized with whole virion, with nucleocapsids of human cytomegalovirus or with solubilized antigens containing virus envelope proteins. All the three types of immunogens induced the production of humoral antibody as well as cytomegalovirus (CMV)-specific cellular immunity. In immunization experiments envelope antigen was as effective as immunization with whole virion.

Animals↗
PubMed1984

Comparative virulence and immunogenicity of the Towne strain and a nonattenuated strain of cytomegalovirus.

The Towne strain cytomegalovirus and a low-passage strain, Toledo-1, were compared for virulence and immunogenicity in healthy adult male subjects to determine the suitability of the Towne strain for vaccination. Five seropositive subjects who received the Toledo-1 strain developed infections ranging in severity from laboratory abnormalities to mild mononucleosis syndromes (mean incubation, 4.7 weeks). None of the four seronegative subjects receiving the Towne strain developed systemic infection, but all developed delayed local reactions at the injection sites. All subjects developed cytotoxic lymphocyte responses specific to cytomegalovirus, usually HLA-restricted, but these were of greater magnitude and duration in the Toledo-1 recipients. The latter also developed natural killer cell and interferon responses, atypical lymphocytosis, inversion of helper/suppressor cell ratios, and depressed responses to T-cell mitogens, none of which occurred in Towne strain recipients. The results further substantiate the avirulence and immunogenicity of the Towne strain cytomegalovirus.

Adult↗
PubMed1984

The importance of immunologic factors in the pathogenesis of encephalomyocarditis virus induced diabetes in mice.

The pathogenesis of EMC virus induced diabetes has generally been thought to be caused by direct cytopathic effect of the virus on beta cells with susceptibility or resistance dictated primarily by the density of viral receptors on the beta cells of different individuals. The histological finding of insulitis, our demonstration of a protective effect of immunosuppression with ALS or anti-theta antibody and silica supports host immune factors as important determinants of susceptibility. A critical role of the immune system might be mediated by autoimmune destruction of EMC-virus infected beta cells. In susceptible strain mice treated with low dose cyclophosphamide to deplete suppressor cells, which may halt the autoimmune process and allow recovery, a prolonged period of hyperglycemia was demonstrated as compared to controls. Bone marrow exchanged between susceptible and resistant strains was also found to alter susceptibility. "B mice", deficient in T lymphocytes, when infected with EMC virus had a decreased incidence of diabetes. Susceptibility to EMC diabetes may be dictated by the autoaggressive response of host immune system to beta cells altered by EMC virus infection.

Animals↗
PubMed1983

The cultivation of human rotavirus, strain 'Wa', to high titer in cell culture and characterization of the viral structural polypeptides.

The structural proteins of the 'Wa' (serotype 2) strain of human rotavirus have not been described previously. Single-cycle virus growth in MA-104 cells using 5 micrograms/ml of trypsin in the growth medium was rapid with maximal viral yields (approximately 10(6) PFU/ml) obtained 10-12 h post-infection. There was a continuous progression of cytopathic effect (CPE) from 6- to 5-h post-infection. Under conditions of multiple-cycle growth, a greater concentration of trypsin (40 micrograms/ml) in the growth medium was required to obtain rapid progression of CPE and production of a high titer (approximately 10(7) PFU/ml) of infectious (double-shelled) virus. Single- and double-shelled virions were separated by isopycnic centrifugation in CsCl and analyzed by SDS-PAGE. Five proteins with molecular weights of 116,000, 92,000, 88,000, 84,000 and 41,000 were identified as components of the inner shell and four proteins with molecular weights of 60,000, 38,000, 32,000 and 27,000 were located in the outer shell.

Animals↗
PubMed1983

Supernatant virus release as a differentiating marker between low passage and vaccine strains of human cytomegalovirus.

The ratio of CMV virus released into the supernatant per infected human fibroblast was studied for three laboratory strains and seven fresh isolates. The former all gave ratios over one whereas the latter gave ratios less than one. This phenomenon may serve as a marker of high passage attenuated virus, as about 25 passages were required in case of one strain to change this property.

Cells, Cultured↗
PubMed1983

Response of mice to rotaviruses of bovine or primate origin assessed by radioimmunoassay, radioimmunoprecipitation, and plaque reduction neutralization.

Sera from (i) gnotobiotic BALB/c, CD-1, and CFW mice and (ii) conventional BALB/c mice were evaluated by radioimmunoassay, radioimmunoprecipitation, and plaque reduction neutralization, using the Wa, SA-11, and WC-3 (bovine) strains of rotavirus as the detecting antigens. The gnotobiotic mice had no antirotavirus antibody detectable by radioimmunoprecipitation and no neutralizing antibody at a dilution of 1:50 by plaque reduction neutralization. All sera from the conventional mice had rotavirus-specific antibodies detected by radioimmunoassay and by radioimmunoprecipitation at serum dilutions of 1:50 and 1:10,000, respectively. The antibodies were directed against viral proteins p116, p94, p88, and p84 of all three viruses, but had no neutralizing activity against heterologous rotaviruses at a dilution of 1:50. Conventional seropositive mice were parenterally immunized with the Wa, SA-11, or WC-3 strain of rotavirus. An approximate 100-fold increase in rotavirus-specific antibodies was detected by radioimmunoassay, and greater than 20-fold selective neutralization of the immunizing strain of virus was observed. Sera from the mice immunized with Wa virus had antibodies directed against inner and outer capsid proteins of all three rotaviruses. The mouse can be a useful model for studying the immune response to heterologous rotavirus infection; preexisting antibodies presumably directed towards murine rotavirus do not prevent the development of a type-specific immune response to a nonmurine rotavirus.

Animals↗
PubMed1983

Human skin fibroblasts are nonpermissive to coxsackie B4 infection: an age-dependent phenomenon.

Human skin fibroblasts were previously shown to be resistant to coxsackie B4 virus infection. We have cultured fibroblasts from skin and lung tissues of donors of various ages. By a novel method for direct assay of virus absorption and penetration, we have shown that skin fibroblasts from young fetuses are susceptible to coxsackie B4 infection, whereas those from older fetuses, children and adults are not and that this refractoriness is caused by a tissue-specific block to virus penetration.

Adult↗
PubMed1983

Live attenuated varicella vaccine: the KMcC strain in healthy children.

The KMcC strain of live, attenuated varicella-zoster virus vaccine was studied in healthy children as a preliminary step toward varicella vaccine studies with this strain in children with leukemia. Forty-three children were immunized: 26 with the 40th passage vaccine and 17 with the 50th passage. Studies included surveillance for clinical reactivity, oropharyngeal excretion of vaccine virus, viruria, and viremia. Antibody responses were assayed by fluorescent antibody to membrane antigens and immune adherence hemagglutination. Cell-mediated immune responses were assayed by lymphocyte proliferation to varicella-zoster virus specific antigens. There was 100% seroconversion to the KMcC passage 40 and 50 vaccines (by fluorescent antibody to membrane antigen assay). Every child studied developed in vitro lymphocyte proliferation to varicella-zoster virus antigens. Papular skin lesions, probably vaccine related, occurred in 31% of the 40th passage vaccinees but in only 6% of the 50th passage vaccinees. The 50th passage KMcC strain vaccine is sufficiently immunogenic and safe to initiate clinical studies with leukemia patients.

Adolescent↗