Measles inclusion-body encephalitis caused by the vaccine strain of measles virus.
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We report a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease. During hospitalization, a primary immunodeficiency characterized by a profoundly depressed CD8 cell count and dysgammaglobulinemia was demonstrated. A brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscopy revealed inclusions characteristic of paramyxovirus nucleocapsids within neurons, oligodendroglia, and astrocytes. The presence of measles virus in the brain tissue was confirmed by reverse transcription polymerase chain reaction. The nucleotide sequence in the nucleoprotein and fusion gene regions was identical to that of the Moraten and Schwarz vaccine strains; the fusion gene differed from known genotype A wild-type viruses. (+info)
Sex differences in antibody- and cell-mediated immune response to rubella re-immunisation.
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Antibody (AMI) and cell-mediated (CMI) immunity to rubella virus (RV) were evaluated in healthy adolescent males (n = 11) and females (n = 28) undergoing routine reimmunisation with RA27/3 strain RV as a component of measles-mumps-rubella (MMR) vaccine. Blood samples were collected just before and at 2, 4 and 10 weeks after MMR. While there were no sex differences before MMR and at week 10 after vaccination, levels of specific IgG determined by whole RV enzyme immunoassay were found to be significantly higher in males at weeks 2 and 4, suggesting brisker onset of recall AMI. Analysis of RV protein-specific IgG by immunoblot assays also revealed that while there were no notable sex differences in the distribution of E1-specific antibodies, more males produced E2-specific antibodies whereas more females produced C-specific antibodies after immunisation. Analysis of CMI with whole inactivated RV and a panel of RV synthetic peptides in lymphocyte proliferation assays revealed a brisker onset of CMI in males which paralleled that observed for AMI. The numbers of RV antigens recognised by males were significantly higher at weeks 2 and 4. Also, mean and median stimulation indices measured at weeks 2 and 4 for certain peptides, including two known to contain overlapping antibody neutralisation domains and T-cell epitopes, E1(213-239) and E1(254-285), were also found to be significantly higher in male subjects. These observations suggest that there are hormonal influences on RV-specific immunity which might result in differential handling of RV and, hence, may partially explain why females are more predisposed to adverse outcomes of rubella infection and immunisation. (+info)
Sex-associated differences in the antibody-dependent cellular cytotoxicity antibody response to measles vaccines.
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In some countries, excessive non-measles-related mortality has been observed among female recipients of high-titer measles vaccines. We determined if differences in the immune response to measles vaccines underlie the excessive female mortality by measuring the measles virus (MV)-specific antibody-dependent cellular cytotoxicity (ADCC) antibody response in 65 3-year-old Gambian children immunized with Edmonston-Zagreb medium-titer (EZ) or Schwarz standard vaccines during infancy. Among the 20 females and 22 males with undetectable anti-MV antibodies at the time of immunization, females had significantly lower ADCC than males (median cytotoxicities of 1/100 serum dilutions = 8.4 and 12%, respectively; P = 0.04). This sex-associated difference was present only among the six female and seven male recipients of EZ vaccine (median cytotoxicities = 5.1 and 19.0%, respectively; P = 0.02). There were no significant sex-associated differences in neutralizing antibody activity. Decreased ADCC antibody activity may contribute to the lower survival rate observed in females receiving high-titer measles vaccination. (+info)
Global measles control and regional elimination, 1998-1999.
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In 1989, the World Health Assembly adopted the goal of reducing measles morbidity and mortality by 90% and 95%, respectively, by 1995, compared with estimates of the disease burden in the prevaccine era. In 1990, the World Summit for Children adopted a goal of vaccinating 90% of children against measles by 2000. Three regions of the World Health Organization (WHO) have targeted elimination: in 1994, the American Region (AMR) targeted elimination by 2000; in 1997, the Eastern Mediterranean Region (EMR) targeted elimination by 2010; and in 1998, the European Region (EUR) targeted elimination by 2007. This report updates progress since 1997 toward global measles control and regional elimination of measles, and includes vaccination coverage and disease surveillance data received by WHO as of August 14, 1999. Data for 1998 suggest that routine measles vaccination coverage has declined in some regions, the number of countries reporting cases and coverage to WHO has decreased, and measles continues to be an important cause of morbidity and mortality. (+info)
A simple model for complex dynamical transitions in epidemics.
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Dramatic changes in patterns of epidemics have been observed throughout this century. For childhood infectious diseases such as measles, the major transitions are between regular cycles and irregular, possibly chaotic epidemics, and from regionally synchronized oscillations to complex, spatially incoherent epidemics. A simple model can explain both kinds of transitions as the consequences of changes in birth and vaccination rates. Measles is a natural ecological system that exhibits different dynamical transitions at different times and places, yet all of these transitions can be predicted as bifurcations of a single nonlinear model. (+info)
Immunization and the American way: 4 childhood vaccines.
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Childhood immunization constitutes one of the great success stories of American public health in the 20th century. This essay provides a historical examination of this topic through 4 particularly important examples: diphtheria, pertussis, polio, and measles. Each case study illustrates how new vaccines have posed unique challenges related to basic science, clinical trial methodology, medical ethics, and public acceptance. A brief comparison of each story to the experience of Great Britain, however, suggests an underlying unity connecting all 4 examples. Whereas the British led the way in introducing formal clinical trial methodology in the field of immunization development, the Americans excelled in the rapid translation of laboratory knowledge into strategies suitable for mass application. Although this distinction appears to have diminished in recent years, it offers insight into the sources of creativity underlying American vaccine development and the corresponding difficulties sometimes created for utilizing vaccines fruits rationally. (+info)
Neutralization of measles virus wild-type isolates after immunization with a synthetic peptide vaccine which is not recognized by neutralizing passive antibodies.
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The sequence H379-410 of the measles virus haemagglutinin (MV-H) protein forms a surface-exposed loop and contains three cysteine residues (Cys-381, Cys-386 and Cys-394) which are conserved among all measles isolates. It comprises the minimal sequential B cell epitope (BCE) (H386-400) of the neutralizing and protective MAb BH6 that neutralizes all wild-type viruses tested. The aim of this study was to design synthetic peptides which induce neutralizing antibodies against MV wild-type isolates. Peptides containing one or two copies of T cell epitopes (TCE) and BCEs of different lengths (H386-400, B(CC); H379-400, B(CCC)), in different combinations and orientations were produced and iteratively optimized for inducing neutralizing antibodies. Peptides with the shorter BCE induced sera that cross-reacted with MV but did not neutralize. The longer BCE containing the three cysteines (B(CCC)) and two homologous TCE were required for neutralization activity. These sera neutralized wild-type strains of different clades and geographic origins. Neutralizing serum was also obtained after immunization with human promiscuous TCEs. Furthermore B(CCC)-based peptides were fully immunogenic even in the presence of pre-existing MV-specific antibodies. The results suggest that subunit vaccines based on such peptides could potentially be used to actively protect infants against wild-type viruses irrespective of persisting maternal antibodies. (+info)
Limitations of in vivo IL-12 supplementation strategies to induce Th1 early life responses to model viral and bacterial vaccine antigens.
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The limited induction of Th1 and cytotoxic immune responses is regarded as the main reason for the increased susceptibility to intracellular microorganisms in early life. Recently, in vitro IL-12 supplementation was shown to enhance the limited IFN-gamma release of measles-specific infant T cells. Using a series of IL-12 delivery systems, we show here that in vivo IL-12 supplementation may enhance early life murine Th1 responses to two model vaccine antigens, measles virus hemagglutinin and tetanus toxin peptide. However, this required multiple repeat injections of recombinant rIL-12, which were poorly tolerated in young mice. Local IL-12 delivery by an IL-12 expressing canarypox vector proved safe but failed to modulate vaccine responses. An IL-12 DNA plasmid or a CD40L DNA plasmid efficiently enhanced neonatal Th1 responses to measles hemagglutinin DNA vaccine. However, both plasmids only enhanced Th1 responses to DNA and not to peptide, protein, or live viral vaccines. Thus, inducing adult-like Th1 responses may be achieved in vivo by inducing (CD40L) or substituting for (IL-12 supplementation) optimal activation of neonatal APC. However, these immunomodulatory effects appear limited to certain antigen-presentation approaches and may not be broadly applicable to vaccines. (+info)