Search PubMed⌕ Search

Biomedical subjects

T J Wiktor

Publications and source records attributed to T J Wiktor.

At least 55 records · Page 3Linked to original sources
PubMed1978

Development and clinical trials of the new human rabies vaccine of tissue culture (human diploid cell) origin.

A new type of rabies vaccine for human prophylaxis was developed by workers at the Wistar Institute, Philadelphia, Pa. Vaccine is prepared from rabies virus infected tissue cultures of human diploid cells and is inactivated following concentration and purification of virus. Vaccine is being successfully used for prophylactic and postexposure treatment in humans with reduced number of doses and is virtually free from adverse reactions associated with the use of other types of rabies vaccines.

Antibody Formation↗
PubMed1978

Comparative study on antibody determination by different methods in sera of persons vaccinated with HDCS-vaccine.

The comparative studies undertaken by 7 laboratories in 6 countries show that the calculation I.U.s did not as anticipated minimize but actually enhanced the variability of results of Rabies antibody estaminations in the sera of HDCS vaccines. The high biological variance in the method(s) may not have been considered by individual laboratories and any neglect of fundamental biostatistical laws, unfortunately, diminishes the theoretical advantage of using the "International Standard (I.S.)" as a "tertium comparationis". Perhaps the intrinsic variability of the I.S. should be re-evaluated and it is conceivable that a pure IgG fraction of Rabies antiserum would show less variability. Intralaboratory variation might be reduced by agreeing that only a geometric mean of the I.S., and not a single value obtained in an individual test, should be used for calculation of I.U.s. Application of the principles of biochemical and pharmacological methods, such as test-to-test control of the I.S. and its analytical variances might well enhance the reproducibility of the results. MNT, RFFIT, PRT and CFT were unable to detect antibodies in HDCS vaccinees until 7 days after the first vaccination. The establishment of methods for detecting early antibody requires further investigation.

Antibodies, Viral↗
PubMed1977

Suppression of cell-mediated immunity by street rabies virus.

Mice lethally infected with street rabies virus failed to develop cytotoxic T cells specific for rabies virus-infected target cells, whereas high levels of cell-mediated cytotoxicity (CMC) were generated after nonfatal infection with the attenuated high egg passage (HEP) or ERA rabies virus strains. Furthermore concurrent infection with street, but not with HEP, rabies virus suppresses development of a primary (but not a secondary) CMC response specific for influenza virus. No cross-reactivity is found between effector T-cell populations from mice immunized with HEP or with influenza virus. It thus appears that street rabies virus, which is not known to replicate in the cells of immune system, induces some general defect in the primary CMC lymphocyte response, though restimulation of memory T-cell populations is unimpaired and there is no defect in antibody formation. Development of fatal rabies may reflect the operation of this selective immunosuppressive mechanism.

Animals↗
PubMed1977

In vitro evidence of cell-mediated immunity after exposure of mice to both live and inactivated rabies virus.

Mice exposed to live or beta-propiolactone-inactivated rabies virus generated a strong, specific cell-mediated cytotoxic response which was generally maximal 6 days after inoculation. Release of 51Cr was apparently a function of immune thymus-derived lymphocytes (T cells) because it was abrogated by prior incubation of spleen cells with anti-thymus antiserum and complement but was undiminished by passage of spleen cells through nylon-wool columns. Cytotoxicity was always maximal for interactions in which thymus-derived cells and targets shared H-2 genes but, unlike the situation found in other assays of this type, considerable lysis of allogeneic, virus-infected target cells may also occur. Perhaps the most significant finding from these experiments is that an inactivated virus has been shown to stimulate a potent cytotoxic thymus-derived cell response. Manipulation of this experimental model may allow analysis of the antigens required for stimulation of cell-mediated immunity. A more practical consequence may be the development of more rational protocols for postexposure vaccination against rabies. Prior treatment of mice with antirabies antibody severely depressed the generation of cell-mediated immunity.

Animals↗
PubMed1977

Induction and biological properties of defective interfering particles of rabies virus.

A method for obtaining large quantities of defective interfering (DI) rabies virus particles that fulfill all the criteria delineated by Huang and Baltimore (1970) is described. The purified rabies DI virion was found to be much shorter (60 to 80 nm) than the complete virion (180 nm) and to have a viral genome of about half the size of normal rabies RNA but with all of the structural proteins of standard virions. Rabies DI virions were noninfectious for both cells in culture and for animals. As determined by in vitro and in vivo techniques, interference with the replication of standard virus was specific to rabies virus. The possible role of rabies DI virion in the pathogenicity of rabies virus infection and in the establishment of attenuated strains for use as live rabies vaccines is discussed.

Animals↗
PubMed1976

Role of interferon in prophylaxis of rabies after exposure.

Rhesus monkeys were completely protected from rabies by a single dose of experimental, highly concentrated, rabies virus vaccine prepared from virus propagated in cultures of human diploid cells and administered several hours after infection with street rabies virus. Protection seemed to be related to the high antigenicity of the vaccine and to its ability to induce interferon in vaccinated animals. Only partial protection was afforded by one or three inoculations of less concentrated vaccines that were prepared from cultures of human diploid cells or primary hamster kidney cells and that were not capable of inducing interferon. The level of virus-neutralizing antibody induced by vaccination could not be correlated with the final outcome of the disease. The simultaneous inoculation of vaccine and interferon inducers (polyribocytidylic acid homopolymer pair or Newcastle disease virus) did not improve the results obtained with vaccine along, a fact which indicates that factors other than interferon and antibody may play an important role in the treatment of rabies after exposure.

Animals↗
PubMed1976

Immunization schedules for the new human diploid cell vaccine against rabies.

Clinical and antibody responses of human volunteers to four different serial production lots of human diploid cell vaccine (HDCV) each with a different antigenic value are described. Three to four doses of HDCV administered over a period of 14 days produced high levels of virus neutralizing antibodies with an average titer up to 20 times higher than the titer elicited by four doses of duck embryo vaccine. Antibodies were still present one year after completion of vaccination. Only minimal differences in antibody response could be observed between groups receiving vaccines of different antigenic values. Untoward reactions to the vaccine were few. The possibility of using the vaccine as part of postexposure human prophylaxis against rabies is discussed.

Animals↗
PubMed1975

Pathogenesis of rabies in immunodeficient mice.

The HEP and ts2 strains of rabies virus inoculated intracerebrally into adult mice normally cause clinically inapparent infection. In the experiments described, this is converted into a lethal infection by immunosuppression with cyclophosphamide, which also prevented induction of immunity with vaccine. Lethal infection of HEP-inoculated mice was also observed in mice treated with antihymocytic serum, and in athymic (BALB/c-nu) nude mice.

Animals↗
PubMed1974

Rhabdovirus replication in enucleated host cells.

Infection of enucleated TC-7 monkey cells with rabies virus resulted in the synthesis of virus-directed RNA and the production of rabies antigens but not of infectious virus. The yield of infectious vesicular stomatitis virus from enucleated TC-7 cells, on the other hand, was almost as high as that from intact cells. Inhibition of the mitochondrial functions of enucleated cells by treatment with ethidium bromide did not influence the development of rabies antigens or the production of infectious vesicular stomatitis virus.

Animals↗