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PubMed2006

Rapid diversification of measles virus genotypes circulating in Morocco during 2004-2005 epidemics.

Measles virus strains circulating in six different regions in Morocco during 2004-2005 were analysed. They were genotyped using two different methods: the recently developed method based on real-time PCR amplification and melting curve analyses, and the conventional method based on nucleic acid sequencing and phylogenetic analysis of 456 nucleotides of the 3'-region of the nucleoprotein (N) gene sequence. Five genotypes (A, B3.2, C2, D7 and D8) were shown to be circulating during this period. Previous studies on measles virus genotypes in Morocco (1998-2003) showed that only the genotype C2 was present and was considered to be endemic. Sequence comparison of the 2004-2005 viruses with other measles strains suggests that measles strains belonging to genotype B3.2 were probably imported from West Africa, whereas those belonging to genotypes D7 and D8 were imported from Europe. These studies which identify the route of importation of measles are important for developing strategies for measles elimination in Morocco.

Disease Outbreaks↗
PubMed2001

CDw150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus.

Natural isolates of measles virus readily infect several lymphocyte cell lines. These viruses appear to use a receptor other than CD46, the molecule to which most laboratory strains of virus bind. Methods used to identify and characterize this lymphocyte receptor for measles virus are described in this study. A binding assay with a soluble form of measles virus H protein demonstrated that B-cell lines, activated with Epstein-Barr virus, or T cells, transformed with human T-cell leukemia virus, exhibit this receptor on their cell surfaces. On the other hand, resting lymphocytes, monocytes, or immature leukocytes either failed to express or possessed reduced levels of this receptor. A cDNA library derived from B95-8 marmoset B-cell lines was used to identify this receptor through expression cloning. This molecule was shown to be CDw150, which is also known as the signaling lymphocytic activation molecule (SLAM). When the lymphocyte receptor was expressed in Chinese hamster ovary (CHOP) or human embryonic kidney (293T) cells, these cells became susceptible to lymphotropic as well as laboratory strains of measles virus. Binding assays confirmed that either lymphotropic or laboratory strains of measles virus could adhere to human or marmoset CDw150, but interaction with the mouse homolog was weak. These infections were independent of the presence of CD46 on the host cell surface. Interaction of measles virus with CDw150(SLAM) could explain the immunosuppressive properties of this virus.

Amino Acid Sequence↗
PubMed1983

Post measles blindness.

Post Measles Blindness occurs in developing countries in 1% of all children with measles and is caused by the interaction of the three factors: measles, malnutrition and treatment. Prevention is to be achieved by an attack on each of these factors; immunisation against measles, improvement of the nutritional status and the application of eye ointment to children with measles are all needed in order to eradicate Post Measles Blindness.

Blindness↗
PubMed1979

Detection of measles virus antigen(s) in peripheral lymphocytes from patients with subacute sclerosing panencephalitis.

Peripheral blood lymphocytes from 5 patients with subacute sclerosing panencephalitis (SSPE) were stimulated with phytohemagglutinin (PHA) and analyzed for the presence of the measles virus antigen(s) by immunofluorescence (IF). For detection of viral antigen fluorescein-conjugated globulins from SSPE patients or from measles convalescents both with high anti-measles titer were used. Peripheral blood lymphocytes from 5 children with measles were used as a positive control. Measles virus antigen(s) were localized in PHA-transformed lymphocytes in all SSPE patients. The present results indicate that in SSPE measles-like virus infection may be found not only in the central nervous system, but also in the circulating lymphoid cells.

Adolescent↗
PubMed1992

Underestimation of the incidence of measles in a population of French children.

Data on titres of specific antibodies against measles virus and information given by families and physicians were analysed in 133 vaccinated and 117 unvaccinated children. Only 2 of the 133 vaccinated children reported a history of measles, while 131 had detectable levels of antibodies. Measles antibodies were detected in 102 (87.2%) of the unvaccinated children, but a history of measles diagnosed clinically by a physician was reported in only 42 of them. These findings suggest that subclinical cases of measles are possible and contribute to the high circulation of the measles virus in the child population in France.

Adolescent↗
PubMed1992

The immune response to measles virus in mice. T-helper response to the nucleoprotein and mapping of the T-helper epitopes.

The T-helper response to the measles virus nucleoprotein (NP) has been studied in mice. The T-cell proliferative response was measured in lymphocytes from mice immunized with either a vaccinia measles-NP recombinant virus or a mouse neuro-adapted measles virus. A T-cell response was obtained with lymphocytes from H2d or H2k mice when stimulated with either measles virus or the NP expressed in bacteria. The response was CD4+ specific. The T-helper epitopes were mapped using truncated NP peptides. The major epitopes in both H2d and H2k mice were determined to be between amino acids 67-98. A further T-cell epitope (between amino acids 457-525) was identified when H2d mice were immunized with measles virus. Studies to quantitate the precursor cells for these epitopes confirmed that the region 67-98 of NP was immunodominant in both haplotypes immunized with the vaccinia-NP recombinant virus, whereas an additional major epitope was observed in the measles virus-infected H2d mice. The primary structure of the epitopes determined here are compared to predicted T-cell epitope motifs.

Amino Acid Sequence↗
PubMed1987

Measles (rubeola) infection in a hospital setting.

Although acquisition of measles infection in medical facilities is well documented, hospital outbreaks have been rare. During a recent community measles epidemic, one patient and four employees of the Mary Hitchcock Memorial Hospital developed the disease. Two of the employees were born before 1956, the year recommended by the Centers for Disease Control as an appropriate cutoff year for routine measles vaccination. Screening of 456 hospital employees for measles immunity demonstrated a 5% incidence of susceptibility in 135 individuals born between 1950 and 1956. This experience demonstrates the significant potential for the spread of a community measles outbreak into the hospital setting. Because of the high transmissibility of this disease and its potentially serious consequences in hospitalized patients, we suggest that all hospital employees born after 1950 who have significant patient contact should have documented immunity against measles.

Adolescent↗
PubMed1995

Antibodies to measles, mumps and rubella in UK children 4 years after vaccination with different MMR vaccines.

Persistence of antibodies 4 years after vaccination with measles, mumps and rubella (MMR) vaccine from three different manufacturers was compared in 475 children who received a single injection of vaccine when aged 12-18 months. Antibodies to measles and mumps were measured using a plaque reduction neutralisation assay; rubella antibodies were measured by radial haemolysis and latex agglutination. Children given MMR vaccine containing the Urabe mumps strain were less likely to be antibody negative than those given the Jeryl Lynn mumps strain (39/266, 15% vs 39/204, 19%, p = 0.048). However, the relatively high proportions in both groups without detectable mumps neutralising antibody suggests the probable need for a second dose in order to achieve mumps elimination. No significant differences were found in the proportions with detectable antibody to measles between vaccines containing the Schwarz and the Enders-Edmonston strains. Overall, only 3% of vaccinees were without detectable measles antibody, although a further 28% had a level below 200 mille International Units, the putative protective level for clinical measles. Geometric mean titres (GMTs) to measles were twofold higher in girls vaccinated after than before 14 months of age; GMTs in boys were intermediate and showed no age effect. Over 99% of vaccinees were seropositive to rubella, confirming the excellent immunogenicity of the RA 27/3 rubella strain and the potential for elimination of rubella with a single dose strategy.

Antibodies, Viral↗
PubMed1986

Adaptation of a commercially available indirect fluorescent antibody slide test for measuring measles-specific immunoglobulins.

A commercially available indirect fluorescent antibody (IFA) test was evaluated for the determination of measles-specific immunoglobulins G and M (MIgG, MIgM). The IFA test detected fourfold rises of MIgG in 34 of 35 (97%) cases of measles confirmed by complement fixation or hemagglutination inhibition. In determining immune status, MIgG-IFA correlated with hemagglutination inhibition in 22 of 23 (96%) cases. The IFA test detected MIgM in only 11 of 34 acute-phase sera collected within 5 days of the reported onset of rash and in the convalescent specimens of another 13 of the 35 specimens. The IFA test is an effective method for the conventional diagnosis of measles and for determining immune status. This IFA test has a limited role as a rapid diagnostic test for measles when used to detect measles-specific MIgM in acute-phase sera obtained from patients with suspected measles.

Agglutination Tests↗
PubMed2005

Potency estimation of measles, mumps and rubella trivalent vaccines with quantitative PCR infectivity assay.

The quantitative PCR infectivity assay is a combination of virus propagation and quantitative PCR. Previously [Schalk JAC, van den Elzen C, Ovelgonne H, Baas C, Jongen PMJM. Estimation of the number of infectious measles viruses in live virus vaccines using quantitative real-time PCR. J Virol Methods 2004;117:179-87.], we used this assay to estimate the titer of infectious measles virus in trivalent, live, measles, mumps, rubella vaccines (MMR). Here we describe the further improvement and development of the assay for simultaneous potency estimation of measles, mumps and rubella viruses. The potency of measles and mumps virus is estimated within one assay after 1 day of cell culture. The potency of rubella virus is estimated in a separate assay after 2 days of cell culture. Compared to conventional CCID50 and plaque assays, the quantitative PCR infectivity assay has the advantage in being fast because the assay is not dependent on the formation of cytopathic effect. Furthermore assay design is simplified: serological neutralization can be omitted because PCR is virus-specific and, under the conditions used, the individual components of trivalent measles, mumps, rubella vaccines do not interfere with each other. The assay was validated and compared to the performance of a plaque assay.

Animals↗
PubMed2004

Synthesis of the measles virus nucleoprotein in yeast Pichia pastoris and Saccharomyces cerevisiae.

The development of a simple, efficient and cost-effective system for generation of measles virus nucleoprotein might help to upgrade reagents for measles serology. The gene encoding measles nucleoprotein was successfully expressed in two different yeast genera, Pichia pastoris and Saccharomyces cerevisiae, respectively. Both yeast genera synthesized a high level of nucleoprotein, up to 29 and 18% of total cell protein, in P. pastoris and S. cerevisiae, respectively. This protein is one of most abundantly expressed in yeast. After purification nucleocapsid-like particles (NLPs) derived from both yeast genera appeared to be similar to those detected in mammalian cells infected with measles virus. A spontaneous assembly of nucleoprotein into nucleocapsid-like particles in the absence of the viral leader RNA or viral proteins has been shown. Compartmentalisation of recombinant protein into large compact inclusions in the cytoplasm of yeast S. cerevisiae by green fluorescence protein (GFP) fusion has been demonstrated. Sera from measles patients reacted with the recombinant protein expressed in both yeast genera and a simple diagnostic assay to detect measles IgM could be designed on this basis.

Blotting, Western↗
PubMed2005

Identification of HLA-DRB1-bound self-peptides following measles virus infection.

We developed a B-lymphocyte cell line derived from a measles seropositive individual who was homozygous for the HLA-DRB1*0301 allele. Peptides associated with the HLA-DRB1*0301 protein were purified from this lymphoblastoid cell line after infection with the Attenuvax measles vaccine virus (Merck Research Laboratories, West Point, PA) and with "sham" infection. More than 40 peptide sequences were obtained by nano-scale reversed phase-high performance liquid chromatography coupled to tandem mass spectrometry (nano-LC/MS/MS). These peptides originated from 21 different source proteins--the majority from membrane-bound proteins. Most of the peptides (>73%) bound to HLA-DRB1*0301 appeared to be in lower abundance on measles-infected cells compared to the "sham-infected" cells. However, 26% of the identified peptides seem to have increased expression after measles infection. Measles vaccine virus infection did not change the level of HLA-DR expression. We demonstrate the power of nano-LC/MS/MS in the rapid determination of changes in the spectrum and expression of HLA-DRB1*0301-bound peptides after infection with measles virus. This provides further knowledge of the changes in peptide expression after viral infection and provides a powerful tool for identifying HLA-presented host and viral epitopes in the context of class II HLA molecules.

Alleles↗
PubMed2004

Recombinant measles AIK-C strain expressing current wild-type hemagglutinin protein.

We constructed a recombinant measles virus cDNA, pIC-MVAIK-H/87-K, in which the hemagglutinin (H) gene of the AIK-C vaccine strain was replaced by the wild-type (MVi/Tokyo.JPN/87-K: genotype D3) H gene and the remaining genes were the same as the AIK-C vaccine strain. To investigate the feasibility of the recombinant vaccine strain expressing wild-type H protein instead of the AIK-C H protein, we constructed two recombinant measles cDNA, having Leu (small plaque-type) and Phe (large plaque-type) at position 278 of the F protein. Infectious chimeric virus strains, MVAIK-H/87-K/S (small plaque-type) and MVAIK-H/87-K/L (large plaque-type), were recovered, which were designed to induce small (S) and large (L) plaques in Vero cells. The MVAIK-H/87-K/S and MVAIK-H/87-K/L did not grow at 39-40 degrees C, similar to the original AIK-C strain, and retained the temperature sensitivity (ts) characteristics. They did not induce cytopathic effect (CPE) in Vero cells but produced CPE in B95a cells, similar to the current wild-type measles MVi/Tokyo.JPN/87-K. From the results of Western blotting, the mobility of the H protein of MVAIK-H/87-K/S and MVAIK-H/87-K/L was similar to that of MVi/Tokyo.JPN/87-K. Hyper-immune sera raised by MVAIK-H/87-K/S neutralized all types of current wild strains. Thus, the chimeric measles virus expressing the current wild H protein demonstrated wild-type H properties with ts characteristics of the vaccine strain, indicating that the construction strategy of recombinant measles virus can cope with the hyper-mutated measles virus.

Animals↗
PubMed2005

Follow-up of infants given measles vaccine at 6 months of age: antibody and CMI responses to MMRII at 15 months of age and antibody levels at 27 months of age.

The worldwide elimination of measles is an important target. In developed countries, to control measles outbreaks, immunization from 6 months of age is recommended. In this study, infants (n = 290) who were (1) born to mothers with natural immunity or to vaccinated mothers and (2) previously immunized with Connaught (CLL) or AIK-C measles vaccine at 6 months of age, were evaluated for measles immunity before and after measles-mumps-rubella (MMRII at 15 months of age. Eight weeks after MMRII, 98.9% of infants were seropositive by enzyme immunoassay (EIA) and 70% demonstrated measles specific cellular immunity by blast transformation (BT) of lymphocytes. At 27 months of age, 98.4% of infants had protective antibody levels by plaque reduction neutralization (PRN) test. These results suggest that AIK-C and CLL vaccines elicit durable protective immunity in young infants when used in early immunization programs.

Aging↗
PubMed1977

A measles outbreak among adolescents.

In a May, 1975, outbreak, 147 adolescents, ages 12 to 19 years, were identified as having measles by a physician or school nurse. One junior high school, with an enrollment of 1,122, contributed 131 of the cases. Of the 147 students, 54 were seen by physicians who also supplied their immunization records; 19 of 54 (35%) had received live measles virus vaccine without measles immune globulin, after age one year. The remaining 35 received: killed virus vaccine only (1), K + L (4), L + MIG (4), L at less than 1 year of age (4), L + ? MIG (4), immune serum globulin only, for exposure (6), no vaccine but history of measles previously (9); history uncertain (3). Hemagglutination-inhibition antibody titers were consistent with the diagnosis of acute measles in 11 children. No index case was identified and no secondary cases occured within the families of the 54 cases. This measles outbreak among seemingly immunized adolescents raises a serious question as to the duration of such protection.

Adolescent↗
PubMed1978

Revaccination of previous recipients of killed measles vaccine: clinical and immunologic studies.

Clinical and immunologic studies were performed in association with revaccination with live measles vaccine in 75 adolescents 11 to 14 years after immunization with killed measles vaccine. Ten subjects had local pain with swelling or erythema or both at the injection site; in three, the local reactions were severe and disturbing systemic complaints were also noted. These marked reactions were more common in subjects in whom the interval between the last dose of killed vaccine and the dose of live vaccine of the primary immunization series was less than or equal to 2 months, in subjects with prevaccination serum HAI antibody titers of less than or equal to 5, and in subjects with high measles antigen specific lymphocyte stimulation ratios. Serum complement levels could not be correlated with clinical reactions. Measles specific lymphocyte stimulation ratios were significantly higher in recipients of killed vaccine than in three compara,ive groups, in subjects with a killed-live interval in the initial vaccine series of less than or equal to 2 months as compared with greater than or equal to 3 months, and in subjects with prevaccination HAI antibody titers of less than or equal to 5 as compared with titers greater than or equal to 10. Although both low serum antibody and high measles specific lymphocyte reactivity were associated with marked local reactions, and probably indicative of susceptibility to atypical measles, our findings suggest that exaggerated lymphocyte reactivity is of greater importance in the adverse clinical response.

Adolescent↗
PubMed1982

Measles virus panniculitis subsequent to vaccine administration.

A severe illness developed gradually in a healthy boy following administration of live measles vaccine at age 14 years. Killed measles vaccine had been given at age 2. Panniculitis began near the site of live vaccine injection, extended contiguously to involve the entire upper arm, and then began to appear in distant subcutaneous sites. He was febrile, leukopenic, anemic, and lost weight rapidly. Evidence of a cause-and-effect relationship between the lesions and the measles vaccine included biopsy findings of particles closely resembling measles nucleocapsids and complete virions by electron microscopy, positive fluorescence after staining with two anti-measles nucleocapsid sera, and immunologic aberrations. The lesions regressed after various treatments and completely remitted on two occasions, but recurred. He became severely malnourished and finally died 29 months after the measles vaccination. At autopsy, pannicultitis was found in the subcutis and mesentery, without evidence of involvement of the brain or other vital organs.

Adipose Tissue↗
PubMed1983

Effect of timing of measles vaccination on compliance with immunizations during the second year of life.

In 1976 the recommended time for routine measles immunization was changed from 12 to greater than or equal to 15 months of age. Because of the known decrease in compliance with immunizations given during the second year of life and the scheduling of an additional visit close to the time of the diphtheria-tetanus-pertussis (DTP) booster immunization, the potential benefit from this change might be offset by a decrease in compliance in securing both measles vaccination and DTP booster immunization. A study of the change in immunization compliance was carried out in a county health facility and in a prepaid medical group practice. Charts of 795 infants (395 born before and 400 born after the change) were reviewed to assess the rates of compliance with measles and with DTP immunizations. Administration of measles vaccine at a scheduled time decreased by 10% (0.05 less than P less than 0.06) at the public health facility after the change in 1976 and by 13% at the prepaid group practice (P less than 0.01). This difference evened out in the public health facility patients by age 2 years, but a 9% decrease was still apparent at the prepaid medical group. A similar pattern was seen in compliance with the DTP booster immunization at each site. Any benefit derived by an increased measles seroconversion rate apparently was offset by an overall decrease in compliance for both measles and DTP booster immunizations.

Community Health Services↗