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[Studies on establishment and maintenance of persistent infection with measles virus in NC-37 cell. II. Effect of DNA-synthesis-suppressing factor (DSF) on the production of interferon in NC-37 cell infected with measles virus (author's transl)].

The attenuated strain of measles viruses, Schwarz, CAM-70, or subacute sclerosing panencephalitis (SSPE) virus of measles viruses, Halle, Mantooth was good interferon inducer, but the virulent strain, Edmonston, Toyoshima induced few amount of interferon or not. Furthermore, an inverse relationship seemed to exist between the ability to induce interferon and DNA synthesis suppressing factor (DSF). The attenuated strain or SSPE virus which had not a capacity to produce DSF could induce interferon and establish persistent infection in human lymphoid cell NC-37, while virulent strain did not induce interferon but DSF. Maximum yield of progeny virus was precede the detection of interferon in culture fluids. A persistently infected cells also produced continuously interferon and progeny virus. It is demonstrated that DSF suppressed interferon production by infection of measles virus and that DSF had not an activity like interferon.

Cells, Cultured↗

Measles immunization with further attenuated heat-stable measles vaccine using five different methods of administration.

Further attenuated heat-stable measles vaccine Attenuvax was administered randomly to 109 children using five different methods and a control group (24). Vaccine administration by syringe and needle (0.5 ml) and by jet-injector (0.1 ml) resulted in a high percentage of significant HAI measles antibody titres (greater than or equal to 1:24). Vaccine administration by nose drops (0.5 ml), bifurcated needle or needle planted cylinder did not yield satisfactory levels of serum antibody. Morbidity measured over a period of four weeks after administration showed a moderate increase of respiratory symptoms over the controls. Children who showed a positive tuberculin PPD reaction after BCG immunization did not differ from children with a negative tuberculin reaction in regard to their ability to produce a Kenya. The aim was to find a simpler method of administration of this improved vaccine, suitable for community health workers. The vaccine was shown to be less stable under field conditions than suggested by previous reports.

Antibodies, Viral↗

A new measles mumps rubella (MMR) vaccine: a randomized comparative trial for assessing the reactogenicity and immunogenicity of three consecutive production lots and comparison with a widely used MMR vaccine in measles primed children.

OBJECTIVES: A multicenter, single-blind, randomized, controlled clinical study was conducted in healthy 15-18-month-old children in order to assess the immunogenicity and reactogenicity of three consecutive lots of a new measles- mumps-rubella (MMR) vaccine, GSK MMR. DESIGN: A total of 500 enrolled subjects were randomized into four groups to receive either a single dose of one of the three lots of GSK MMR (three groups--125 subjects in each group) or Merck MMR vaccine (125 subjects). Once clinical consistency had been demonstrated, the data were pooled and compared with the widely used Merck vaccine. Solicited local and general symptoms were recorded using diary cards, and antibody levels were determined using ELISA assays. RESULTS: No differences in the incidence of local and general symptoms or seroconversion rates were seen in the groups receiving different lots of GSK MMR. Compared with Merck MMR, there was a significantly lower incidence of local pain (P<0.001) and swelling (P=0.038) in infants receiving the GSK MMR vaccine. The incidences of all other solicited local and general symptoms were comparable between the two groups. No signs of suspected meningitis were reported. No serious adverse events were reported by the investigator to be related to vaccination. Equivalent seroconversion rates and postvaccination GMTs were observed in the groups receiving the two MMR vaccines. In conclusion, the new GSK MMR vaccine administered in measles-primed children demonstrated satisfactory immunogenicity and safety profiles as good as the Merck MMR vaccine.

Antibodies, Viral↗

Measles vaccination. VIII. The occurrence of antibodies against virus envelope components after immunization with inactivated vaccine. Effects of revaccination with live measles vaccine.

Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8-9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-inhibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable in their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to faccination. 4 vaccinees with low pre-vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by sue of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin.

Antibodies, Viral↗

Successful boosting of a DNA measles immunization with an oral plant-derived measles virus vaccine.

Despite eradication attempts, measles remains a global health concern. Here we report results that demonstrate that a single-dose DNA immunization followed by multiple boosters, delivered orally as a plant-derived vaccine, can induce significantly greater quantities of measles virus-neutralizing antibodies than immunization with either DNA or plant-derived vaccines alone. This represents the first demonstration of an enhanced immune response to a prime-boost vaccination strategy combining a DNA vaccine with edible plant technology.

Administration, Oral↗

The virtual elimination of rubella and mumps from the United States and the use of combined measles, mumps and rubella vaccines (MMR) to eliminate measles.

The measles elimination effort, which began in 1978, has made dramatic contributions to the virtual elimination of rubella and congenital rubella syndrome (CRS) and the control of mumps in the USA. The use of combined MMR vaccine has resulted in immunization levels at school entry in excess of 95% against each of these diseases. As a result, record low levels of rubella, CRS, and mumps were reported in 1984. Continued use of MMR, along with improved surveillance and aggressive response to outbreaks, can be expected to eliminate rubella and mumps as well as measles.

Cost-Benefit Analysis↗

[Persistence of the measles antigen in the central nervous system of monkeys infected with clonal variants of the L-16 vaccinal strain of the measles virus].

The time of persistence of measles antigen was studied in Macaca mulatta and green monkeys inoculated intracerebrally with the vaccine L-16 strain of measles virus and its two genetically homologous variants. Two clones differing in their neurovirulence were used. The results of the study showed correlation between the time of the antigen persistence in the central nervous system and the severity of morphological changes.

Animals↗

Seroconversion rates and measles antibody titers induced by measles vaccination in Latin American children six to 12 months of age.

A collaborative study was conducted to determine how 2,042 infants responded serologically to measles vaccination in six study areas and to help define the optimal age for measles vaccination in children of Latin America. The results suggest that local factors affect the seroconversion rate and that a success rate of 90% can be attained if initial vaccination is given at nine to 11 months of age, depending on the area. Post-vaccination titers also varied, and higher titers were generally observed in groups with higher seroconversion rates.

Age Factors↗

Optimal age for vaccinating Nigerian children against measles. I. Neonatal antibody profile and subsequent susceptibility to measles.

The decline of maternally acquired haemagglutination inhibiting antibodies against measles virus in Nigerian children born in Lagos was studied. At birth all the 303 children whose cord blood serum was tested had measurable antibodies. The antibody titre remained detectable in all the children up to four months of age, and in over 90% at five months of age. At six months 65% of the children were without detectable antibodies. At seven and eight months the proportion of children without measurable antibodies was reduced to 50% and 42% respectively, indicating a slight but progressive improvement in the immune status of the children. These findings provide a serological basis for starting anti-measles immunization of Nigerian children at six months.

Age Factors↗

Optimal age for vaccinating Nigerian children against measles. II. Seroconversion to measles vaccine in different age groups.

Ninety-eight children between five and nine months were given measles vaccine. Bloodsamples were taken before and again six to eight weeks after immunization and tested for haemagglutination inhibition antibodies to measles virus. It was found that the sero-conversion rate was significantly lower (p less than 0.05) in infants under seven months than over this age. The results suggest that although some immunized at six months of age show seroconversion, the proportion is too small to justify extensive immunization at this age. It is proposed that children in Lagos should be immunized from the age of eight to nine months.

Age Factors↗

Transgenic mice expressing human HLA and CD8 molecules generate HLA-restricted measles virus cytotoxic T lymphocytes of the same specificity as humans with natural measles virus infection.

Control of primary measles virus (MV) infection in humans and continued maintenance of immune memory that protects against reinfection are mediated primarily through the anti-MV T cell response, as judged by observations of children with defects in antibody formation but competency in making T cells. Further, the failure of T cell responses in those infected with MV most often leads to overwhelming infection. To better define and manipulate the elements involved in human T cell responses to MV, we analyzed the generation of HLA-restricted cytotoxic T lymphocytes (CTL) in a small animal model. Transgenic mice expressing the human class I MHC antigen HLA-B27 in conjunction with human CD8 molecules produced vigorous HLA-restricted CTL responses to MV antigens, paralleling those in MV infection of humans. In addition, such humanized mice generated human CD8 coreceptor-dependent HLA-B27-restricted CTL with the same specificity for recognition of MV fusion (F) peptide RRYPDAVYL as reported for humans during natural MV infection. Neither murine beta(2)-microglobulin nor murine CD8 substituted adequately as coreceptors for the HLA-B27 heavy chain. By contrast, HLA-A2.1-restricted responses to measles could be generated in the absence of expression of human beta(2)-microglobulin or CD8(+) molecules in HLA-A2.1/K(b) transgenic mice. Thus a small animal model is now available for studying strategies for optimizing human CD8(+) T cell responses and for testing vaccines. This model offers the potential, when combined with the newly reported CD46 transgenic mouse model in which MV replicates in cells of the immune system, for uncoding the molecular mechanism of MV-induced immunosuppression.

Animals↗

Passively administered antibody suppresses the induction of measles virus antibodies by vaccinia-measles recombinant viruses.

We have used vaccinia-measles recombinant viruses to study vaccination in the presence of pre-existing antibody. When mice were vaccinated with recombinants expressing either the haemagglutinin (H) or fusion (F) measles virus (MV) proteins, the humoral response to the MV protein was suppressed by passively administered polyclonal antibody. However, individual monoclonal antibodies (H or F) did not affect the response. Mice whose anti-MV antibody response to H or F was initially suppressed by passive administration of anti-MV antibody were revaccinated 120 days later and gave a normal humoral response to the MV proteins. The VV-H recombinant induces a strong class I CTL response in Balb/c mice. This was not affected by the presence of levels of anti-MV antibody which inhibited the humoral response.

Animals↗

Measles immunity testing: comparison of two measles IgG ELISAs with plaque reduction neutralisation assay.

Two commercial IgG ELISAs, one based on recombinant nucleocapsid antigen and one based on cell culture grown native virus antigens, were evaluated for measles immunity testing by comparison with plaque reduction neutralisation test (PRNT). Qualitative results of the two ELISAs showed 92% agreement with those of PRNT. The sensitivity of the two ELISAs was 89.6%. False negative ELISA results were obtained in 10% of sera, mainly sera containing low levels of neutralising antibody. The specificity of both ELISAs was 100%. Measles IgG ELISAs perform adequately for immunity testing, correctly identifying seronegative individuals for vaccination.

Antibodies, Viral↗

Characterization of the measles virus isolated from the brain of a patient with immunosuppressive measles encephalitis.

Two strains of measles virus with different biologic properties were isolated from the brain of a patient with immunosuppressive measles encephalitis. One strain (Oita-1) grew extremely slowly in Vero cells and did not produce any cell-free virions. The other strain (Oita-2) replicated well, and a small amount of cell-free virus was detected from the culture medium and the freeze-thawed homogenate. Neurovirulence of the Oita-1 strain to mice was, however, stronger than that of the Oita-2 strain. Synthesis of the M protein by the Oita-2 strain was not demonstrable in the infected cells when they were labeled for 24 hr; however, a new protein moiety that was smaller in molecular weight than the M protein and that was not precipitated with monoclonal antibody to M protein was demonstrated by pulse-labeling for 1 hr. Antibodies to the M protein, as well as to other proteins, were detected (by immunoprecipitation) in the serum and cerebrospinal fluid of the patient.

Animals↗

Restriction of measles virus gene expression in measles inclusion body encephalitis.

Measles virus (MV) infection in brain tissue of a patient with measles inclusion body encephalitis was characterized by immunologic and biochemical techniques. Of the five major structural proteins of MV, only nucleocapsid (N) protein and phosphoprotein (P protein) were consistently detected in diseased brain areas. In contrast, hemagglutinin protein was seen only occasionally, and no membrane and fusion proteins were found in any of the sections studied. Messenger RNAs (mRNAs) specific for these five viral proteins were detected in all brain extracts examined; however, the mRNAs for the envelope proteins were clearly underrepresented in comparison with lytically infected cells. Only the mRNAs for N and P proteins appeared active in in vitro translations. These findings indicate quantitative differences in the pattern of mRNA expression in brain tissue and a restricted expression of MV envelope proteins in infected cells as observed in subacute sclerosing panencephalitis.

Brain↗

Oral immunization with recombinant Yersinia enterocolitica expressing a measles virus CD4 T cell epitope protects against measles virus-induced encephalitis.

Immunization via the oral route with an attenuated Yersinia enterocolitica strain expressing a fragment of the measles virus nucleocapsid protein (aa 79-161) via its type III protein secretion system induced a T helper type 1 response in immunized C3H mice, which conferred protection against measles virus-induced encephalitis in a time- and dose-dependent manner.

Administration, Oral↗

Vigorous but short-term gamma interferon T-cell responses against a dominant HLA-A*02-restricted measles virus epitope in patients with measles.

The absolute and relative abundance of major histocompatibility complex class I-presented viral epitopes is important in the induction and maintenance of antiviral cytotoxic-T-lymphocyte (CTL) responses. We demonstrate that the supra-abundant HLA-A*0201-restricted peptide KLWESPQEI of the measles virus nonstructural C protein induces strong gamma interferon CD8(+)-T-cell responses in children with acute measles. However, longitudinal analysis indicates that these responses are only short-lived. Thus, some viral epitopes that can be immunodominant during primary infection may fail to establish memory CTL responses.

Epitopes, T-Lymphocyte↗