STUDIES ON THE LIVE ATTENUATED MUMPS VIRUS VACCINE
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Abstract:
1) In comparative experiments with Enders strain adapted to the chorio-allantoic cavity of the developing chick embryo and the newly isolated Towata strain of mumps virus, it was noticed that Enders strain was considerably attenuated. Towata strain showed a wide host range of tissue culture cells, mild virus growth in suckling mouse brains and high pathogenicity for the parotid glands of monkeys.2) Attenuated Enders Strain was used for an inhalation test with monkeys as the live mumps vaccine. All monkeys showed good antibody responses without clinical manifestations.3) Passage of the virulent Towata strain in the chorio-allantoic cavity of the embryonated egg was successful. During many passages, Towata strain lost the infectivity to various cells, acquiring biological characteristics similar to Enders strain.Keywords:
Embryonated
Infectivity
Attenuated vaccine
Strain (injury)
Mumps virus
Serial passage
Sendai virus
Sixty-six paired sera from patients suffering from mumps were examined with Sendai and mumps virus particle antigen: 50% showed a rise of complementfixing antibodies to mumps virus particle antigen only and the rest to both antigens. This relationship was further substantiated by the occurrence of both antibodies in a proportion of the sera of 362 blood transfusion donors and 978 sera from antenatal patients. The occurrence of both antibodies in patients' sera is discussed and the conclusion is reached that one of the components of the mumps antigen complex is indistinguishable from the essential components of the Sendai virus. I am indebted to the Maternity Department of the Edgware General Hospital for supplying the antenatal sera, and to Dr Preston of the Regional Transfusion Centre, Oxford, for the blood donor sera.
Sendai virus
Mumps virus
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Sendai strain of parainfluenza 1 virus previously passed in embryonated eggs was found to be adaptable to the stable line of human conjunctiva cells. Evidence for its multiplication in these cells was based on its capacity to produce typical CPE in 5–7 days throughout 17 serial passages, on its ability to initiate macroscopic plaque formation and on the nature of its single step growth cycle. The adapted virus could be cultivated in either conjunctiva cells or chick embryos. The former was more sensitive to viral infection (ratios of PFU:EIU up to 27) whereas higher virus titers were obtained from the latter.
Embryonated
Sendai virus
Serial passage
Strain (injury)
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Sendai virus
Mumps virus
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Summary The immunological relationships between mumps virus and parainfluenza viruses were investigated with 74, 78 and 80 previously developed monoclonal antibodies directed against five major structural proteins of mumps virus, Sendai virus (a murine parainfluenza type 1 virus) and parainfluenza type 3 virus. These monoclonal antibodies were reacted with the three viruses, with parainfluenza type 2 virus and with Newcastle disease virus (NDV) in ELISA and immunofluorescence (IF) tests. In addition, immunoprecipitation tests with [35S]methionine-labelled extracellular virions were carried out with cross-reacting monoclonal antibodies. None of all 232 monoclonal antibodies against the three viruses cross-reacted with either parainfluenza type 2 virus or NDV in ELISA and IF tests. In the collection of 74 mumps virus monoclonal antibodies, three directed against the nucleocapsid (NP) protein, polymerase protein, and fusion protein cross-reacted with Sendai virus. Two Sendai virus monoclonal antibodies directed against two different epitopes of the haemagglutinin-neuraminidase (HN) protein cross-reacted with parainfluenza type 3 virus. Six other Sendai virus monoclonal antibodies directed against four different epitopes of the HN protein and one directed against the NP protein cross-reacted with mumps virus. Eight out of 80 monoclonal antibodies directed against parainfluenza type 3 virus cross-reacted with Sendai virus. One was directed against the HN protein, four were directed against a minimum of two epitopes of the matrix protein and three were directed against three different epitopes of the NP protein. The different cross-reactions found show that Sendai virus is antigenically related to both mumps virus and parainfluenza type 3 virus. In contrast, no antigenic relationship could be demonstrated between mumps virus and parainfluenza type 3 virus.
Sendai virus
Mumps virus
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1) In comparative experiments with Enders strain adapted to the chorio-allantoic cavity of the developing chick embryo and the newly isolated Towata strain of mumps virus, it was noticed that Enders strain was considerably attenuated. Towata strain showed a wide host range of tissue culture cells, mild virus growth in suckling mouse brains and high pathogenicity for the parotid glands of monkeys.2) Attenuated Enders Strain was used for an inhalation test with monkeys as the live mumps vaccine. All monkeys showed good antibody responses without clinical manifestations.3) Passage of the virulent Towata strain in the chorio-allantoic cavity of the embryonated egg was successful. During many passages, Towata strain lost the infectivity to various cells, acquiring biological characteristics similar to Enders strain.
Embryonated
Infectivity
Attenuated vaccine
Strain (injury)
Mumps virus
Serial passage
Sendai virus
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It could be demonstrated by immunoelectrophoretic analysis that the host antigen incorporated in the envelopes of Sendai virus cultivated in KB cells (Sendai/KB) is characteristic of these cells and does not occur in the envelopes of the same virus grown in the embryonated hen egg (Sendai/egg). This host antigen appears from the first passage in KB cells and is constantly maintained over subsequent passages. The glycoproteins released by Triton X-100 disruption from Sendai/KB envelopes have a concomitant antigenic specificity for both virus and host. In the case of Sendai/egg virus, exclusively virus-specific macromolecules are also released.
Sendai virus
Embryonated
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Undiluted allantoic fluids were used as inocula for serial passage of a mixture of the PR8 and Lee strains of influenza virus in embryonated eggs. Although wide differences were found in the relative concentrations of the two viruses in the various fluids, the mixture was successfully carried through 52 consecutive passages, and each agent was recovered in an apparently pure culture at the end of the experimental period. Since the two viruses have different growth rates and are capable of interfering with the multiplication of each other, the persistence of both agents during serial passage of the mixture suggests that multiplication of the PR8 and of the Lee viruses may not require the same host factors.
Embryonated
Serial passage
Persistence (discontinuity)
Serial dilution
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Abstract Rat dorsal root ganglia in tissue culture, which contain an interferon‐γ (IFN‐γ)‐like immunoreactive subpopulation of neurons, were infected with paramyxoviruses. Sendai virus caused a substantial neuronal lysis, while the RW strain of mumps virus caused a much less pronounced nerve cell loss. Early during infection, the subpopulation of IFN‐γ‐like immunoreactive neurons was less susceptible to mumps virus. Virus antigen was rapidly lost from surviving IFN‐γ‐like positive neurons infected with Sendai virus, while this remarkable self‐curing effect occurred in both nerve cell populations at later time points after mumps virus infection. By quantitative enzyme‐linked immunosorbent assay (ELISA) technique, increased levels of “neuronal IFN‐γ” were recorded at 10 hr and 30 hr after infection with Sendai and mumps virus, respectively. This study indicates a role for the neuronal IFN‐y‐like molecule in determining the outcome of a viral infection in sensory ganglia.
Sendai virus
Mumps virus
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To test the possibility of recent outbreak of Sendai virus infections among the population of Sendai, this serological survey was intended. Proposal of the work was originally made from the result reported in the previous paper, where most sera obtained from mumps patients at acute stag revealed high antibody titer against Sendai virus when tested in hemagglutination inhibition reaction.An explanation of the fact was the shared antigen between these 2 viruses. An alternative idea was the anamestitic elicitation of Sendai virus antibody with mumps virus. However, both possibilities may finally lead to the same conclusion of shared antigen.Serum specimens were obtained from 260 healthy people in Sendai and divided into two groups, i.e. one of children under 15 years, another of adult over 16 years old. The results obtained so far revealed the following conclusion.1) 73% of children and 89% of adult did not have any antibody titer against Sendai virus when examined on hemagglutination inhibition test.2) High distribution of antibody was found only among children between 4 and 10 years old. Antibody titer of these specimens was also high.3) From 71 healthy children of 6 years old, new serum specimen were obtained to test the cross relationship of Sendai virus with mumps virus. 52% of the tested specimens had the titer against Sendai virus and 82% against mumps virus. Among 37 specimens positive against Sendai, 36 specimens (97%) had the significant titer against mumps virus. Whereas among 58 specimens positive agaiast mumps, 36 (62%) was positive against Sendai virus. Taken together, HAI titer revealed here against Sendai virus was anticipated to have the character provoked by mumps virus. However, critical analysis of this observation was left for further studies
Sendai virus
Mumps virus
Antibody titer
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In suspension tests it could be found, that tyrothricin, isolated from bacteria, possesses an anti-infectious activity against Sendai virus. Concentrations of 10(2) to 10(3) ID50-units of Sendai virus were incubated with 0.5 and/or 1.0 mg tyrothricin per 5 ml for 30 minutes at 37 degrees C (pH 7.5). These mixtures were tested in embryonated eggs and showed a marked decrease of viral infectivity. Tween 80 added after the incubation period leads to an incomplete reactivation of the virus infectivity. According to these results and further preliminary studies on herpes simplex virus we suppose a virustatic effect of tyrothricin also in the case of other lipophilic viruses.
Embryonated
Sendai virus
Infectivity
Incubation period
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