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Mixed infection of Vero cells with measles and vesicular stomatitis viruses gives rise to phenotypically mixed infections virus particles possessing the properties of pseudotypes. Similar results were obtained when vesicular stomatitis virus was used to superinfect a defective measles system.
Vaccine induced measles antibody titers in the Upper Xingu Indians remained at satisfactory levels without evidence of decline over a period of six years without re-exposure. However, in another area, a vaccination program which used a reduced dose of vaccine was only 63% effective. When measles virus was introduced to the latter area a protracted epidemic ensued with 23% of the population becoming ill and six deaths. The deaths occurred exclusively under 13 months or over 40 years of age.
The effect of a wild measles virus circulating in a childhood collective body on the immune status of 80 children has been studied over time. Only using enzyme immunoassay was it possible to fully record and assess the degree of booster effect of the virus on children in case of infection transmission. In 25% cases the increment of antibodies was at the expense of specific IgM antibodies appearing in the sera of children. By the end of the first month 60% of children developed a relative measles immunodepression. Analysis of the index of cell stimulation with phytohemagglutinin in the presence of suppressors enabled us to single out a group of children (30%) with weakly expressed suppressive factor. The observed phenomenon with a high degree of reliability may be used as an index of immune response development.
1. We have demonstrated previously (Harrowe et al., 1990), using a lymphoblastoid cell line that constitutively expresses the substance P receptor (SPR) (Payan et al., 1984, 1986), that this receptor may facilitate measles virus (MV) fusion with these cells. In order to test this hypothesis further, a stable cell line transfected with SPR cDNA has been established, and various stages of MV infection in SPR positive and negative cells compared. 2. Jurkat cells, a human T-lymphoblastoid cell line, were transfected with a cDNA clone encoding the SPR. Cells transfected with only the plasmid were used as controls. Jurkat cells and Jurkat vector control cells (J-vo) failed to demonstrate any detectable 125I-SP binding, whereas a clonally selected population of cells transfected with SPR cDNA (J-SPR) expressed about 50,000 receptors/cell (Sudduth-Klinger et al., 1992). 3. Using the J-vo- and J-SPR-transfected cell lines, the following experiments were conducted to investigate the effect of SPR expression on MV infection. To determine if MV would preferentially attach to J-SPR as compared to J-vo, we absorbed virus to cells at 37 degrees C for various times and measured bound MV using a fluorescence activated cell sorter (FACS). Using this approach, we found that MV bound to a greater degree to J-SPR compared with J-vo. In addition to equilibrium being reached faster for J-SPR, the total amount of bound MV was higher on J-SPR. The effect was greater at lower MOIs, suggesting that there existed multiple binding sites for MV on these cells and that the affinity is higher for those cells expressing the SPR. 4. Since binding does not necessitate a successful viral infection, we needed to know if this difference in binding reflected a difference in infection. This was demonstrated by showing an approximate twofold increase in infected cells after a 2-hr binding period with J-SPR as compared to J-vo at an MOI of 1 in an infectious cell-center assay. Moreover, when both cells types were subjected to continuous infection in culture, J-SPR-infected cells produced a seven- to ninefold increase in measles viral titer in 24 hr as compared with J-vo. The observed increase in viral titer may have resulted in more of the J-SPR cells binding virus, as indicated by our binding and infectious cell-center data, or alternatively, the virus might have entered the J-SPR cells faster and begun replication before the J-vo-infected cells.(ABSTRACT TRUNCATED AT 400 WORDS)
A postvaccination questionnaire and review of student and employee clinic visits were carried out at Notre Dame University in the spring of 1990 after mass campus revaccination with measles or measles-rubella vaccines in the autumn of 1989, in order to assess the incidence of adverse experiences after revaccination. Rates of adverse experiences (AE), which included chiefly local injection site discomfort and flu-like symptoms, among respondents were 6.6% and 13.4%, male and female students, respectively, and 9.3% and 25%, male and female employees, respectively. Rates of joint-related complaints (4%) were lower than reported after primary vaccination, particularly in young adult women. AEs in general, and joint reaction rates in particular, were generally mild and transient, and only 0.23% resulted in a clinic visit. Revaccination of prior vaccinees appears to be associated with relatively low AE rates.
Interleukin-4 (IL-4) is a signature cytokine for T-helper 2 (Th2) type immune responses in humans. However, data on antigen-specific secretion of IL-4 is limited due to difficulties detecting IL-4. We evaluated an IL-4 receptor-blocking assay for the detection of secreted IL-4 in peripheral blood mononuclear cells (PBMC) stimulated in vitro with measles virus (MV) and MV-derived nucleoprotein (N) and phosphoprotein (P) peptides. We recruited 20 healthy subjects, previously immunized with two doses of measles-mumps-rubella-II (MMR-II) vaccine. We evaluated the cellular and humoral immune status of these study subjects by an in vitro lymphoproliferation assay and an enzyme-linked immunosorbent assay (ELISA), respectively. We analyzed the MV-induced and N and P peptide-induced IL-4 levels in PBMC culture supernatants. Using the IL-4 receptor blocking assay, 50% of the subjects were positive for secreted IL-4 in response to MV stimulation, and 5% and 23.1% of study subjects were positive for secreted IL-4 in response to MV-derived N and P peptides, respectively. In contrast, we did not find any positive secreted IL-4 response to MV using conventional ELISA without IL-4 receptor-blocking antibody in our optimization study. Further, we found very low frequencies of IL-4 secreting cells using an alternate ELISpot technique, accounting for only a 5% positive response to MV and no response to P peptide. We propose that the IL-4 receptor-blocking assay is an easy-to-adapt technique for screening antigen-specific immune responses in large-scale population-based studies.
Several types of persistent measles virus infection resulting in lytic infections could be established in a calf kidney cell line, according to the passage level of the substrate and to the virus strain inoculated. Persistent measles virus infection in calf kidney cells was characterized by the limited proportion of infected cells, the large amount of infectant virus, and the alteration of morphological and growth characteristics of the cells. The mechanism of this persistent infection is discussed.
A study to assess chromosomal damage in persons with acute viral diseases was undertaken in view of conflicting reports in the literature concerning such damage. Forty children with measles, mumps, and chickenpox, or who had received measles vaccine, were investigated and compared with a control group of 12 children. No greater incidence of chromosomal abnormalities was found in the study group than in the control group.
The biological characteristics of a measles virus strain (Co-69/pi) isolated from a selected chronically infected calf kidney cell line (K-2) are studied in comparison with those of thw wild parental CO-69 and of the attenuated Schwarz measles virus strain. Co-69/pi is a variant of the parental Co-69 virus and has characteristics of an attenuated strain. Some of the characteristics acquired by the Co-69/pi strain (cytopathogenicity, size of plaques) proved to be stable in the course of passages on a simian substrate. The mechanism having led to the appearance of this variant in the chronically infected cell line are discussed.
Lewis rats were immunized with recombinant vaccinia virus (VV) expressing the nucleocapsid (N), phospho (P), matrix (M), fusion (F), and haemagglutinin (H) proteins of measles virus (MV). Animals developed humoral as well as cell-mediated immune (CMI) responses to the corresponding MV proteins. Rats immunized with recombinants VVN, VVF or VVH survived a MV challenge infection whereas VVP- and VVM-immunized rats were only partially protected. In vivo depletion of CD8+ T lymphocytes did not prevent the protective effect of the N, F or H protein-specific CMI response in rats. VVH and VVF immunization induced neutralizing antibodies, but no such antibodies were detected after VVN immunization. Further investigation of the temporal occurrence of the antiviral antibodies indicated that the observed protection provided by VVN and VVF immunization depends on CD4+ N- or F-specific T cells in the absence of neutralizing antibodies and CD8+ T cells. A role for neutralizing antibodies induced by VVH cannot be ruled out.
Clinical cases of measles have been reported to the Swiss Sentinel Surveillance Network (Sentinella) since June 1986 and measles infections have been monitored by the national laboratory notification system since January 1988. These two surveillance syste
A small plaque mutant with reduced neurovirulence in newborn mice was obtained from Edmonston strain measles virus after propagation for 5 months in NIH3T3 cells. It retained the antigenicity of the parental virus and tended to induce higher neutralizing antibody titers in the adult BALB/c mice. The intracerebral (but not intraperitoneal) inoculation of the live mutant virus one day before prevented the newborn BALB/c mice from encephalitis caused by the intracerebral challenge with the parental strain at a dose of 10-20 LD50. The intracerebral inoculation with the mutant virus whose replication capacity was inactivated by UV-irradiation was ineffective. The protection was not attributed to interferons nor to viral interference. The mechanism remains unknown.
In this study the immunogenicity of recombinant nucleoprotein (Np) administered intranasally or intraperitoneally, and its ability to support a systemic protective anti-virus antibody response was examined, in a mouse model of measles virus (MV)-induced encephalitis. Although both intranasal and intraperitoneal routes of immunisation resulted in priming Np- and MV-specific T-cell responses, the intraperitoneal route was shown to prime for a predominantly IgG2a serum anti-MV antibody response of high avidity, which confered complete protection following intracranial challenge with a neuroadapted strain of MV. On the other hand, intranasal priming resulted in a mixed IgG1, IgG2a serum anti-MV antibody response of low avidity, and only 43% of immunised mice survived following intracranial challenge with the neuroadapted strain of MV. These findings suggest that the route of immunisation in combination with an appropriate adjuvant could influence the induction of a quality antibody response with protective capacity.
The immunity status of 37 cases has been tested at 6 weeks and 3.5 years after vaccination by using gelatin beads agglutination (PA), hemagglutination inhibition (HI) and avidity of specific IgG. The geometric mean titer (GMT) of HI antibody was 34.5 at 6 weeks and had fallen to 17.9 over 3.5 years. On the other hand, GMT of PA antibody was 36.5 at 6 weeks and had increased to 286.0 over 3.5 years. Also, the average of measles specific IgG avidity was 4.5% at 6 week and had increased to 45.4% over 3.5 years. The multiple regression analysis was performed in order to investigate the relationship of HI antibody and avidity to PA antibody. The significant involvement of the HI antibody and avidity to PA antibody (standardized partial regression coefficients; 0.612, 0.726) was recognized and the multiple correlation coefficient was 0.880 (p < 0.001). Hence it was strongly suggested that the increase of PA antibody with time could be dependent on that of IgG avidity.
Real-time PCR has been developed to genotype measles virus (MV) isolates. MV strains circulating in epidemics in Gabon in 1984, Cameroon in 2001, Morocco in 2003, and France in 2004 were investigated. We developed a real-time amplification refractory mutation system PCR (RT-AMRS PCR) using SYBR green fluorescent dye. Six pairs of primers for RT-ARMS PCR were designed to specifically amplify genotypes A, B2, B3.1, B3.2, C2, and D7. Genotypes could be differentiated by melting curve analysis. All strains were also confirmed by direct sequencing. Using the result obtained by direct sequencing and phylogenetic analysis as the reference, the accuracy of MV by RT-ARMS PCR and melting curve analysis was 97%. However, the latter method is more rapid and sensitive than the former method. This method could be a useful tool for molecular epidemiological studies of MV, providing an efficient alternative for large-scale studies.
Measles virus (MV) infection of U937 cell or peripheral blood leukocyte cultures was shown to induce changes in the expression of leukocyte function antigen 1 (LFA-1) and cause marked aggregation of these cells. Addition of selected monoclonal antibodies specific for LFA-1 epitopes that did not neutralize MV in standard neutralization assays were found to block both virus-induced leukocyte aggregation and virus dissemination. These data suggest that MV modulation of LFA-1 expression on leukocytes may be an important step in MV pathogenesis.
Measles in an unvaccinated virgin population exacted a death toll of 4.2% which fell particularly hard on the age groups which would ordinarily be protected by maternal antibody. The organ system most affected was quite variable. When the virus spread to a largely vaccinated village it caused only one death. Herd immunity seemed to protect many who were not vaccinated. Vaccine failed to protect 7.7% of the recipients. Some of these failures may have been due to erroneous record, vaccination in the presence of maternal antibody or inactivated vaccine, but most occurred in a few family groups related by genetics and similar past immunological experience.
The study included 205 children with measles seen after an epidemic outbreak in Distrito Federal during the first six months of 1976. 65.8% of the cases had not been given specific immunization and out of the 70 vaccinated cases (34.2%), one half of them were under one year old and were not given re-enforcement afterwards. The clinical picture suffered no changes in vaccinated children, 40% of infants showed initial exanthema on chest and abdomen with centrifugal distribution and in 41.5% of them, diarrhea appeared during the prodromal period. The most outstanding elements of this epidemic outbreak were the high number of sensible cases and the high percentage of children vaccinated before the age of one year and who were not later given re-vaccination. Indequate handling of the vaccine or combination of vaccine withe gammaglobulin used in 1969 and 1970, are also mentioned as a possibility to explain failures of the vaccine in ths group of well vaccinated children.