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The immune response to matrix (M) protein of measles virus was examined in patients with subacute sclerosing panencephalitis (SSPE) and controls. Antibodies specific for M and nucleocapsid (NC) proteins in 11 serum and 8 cerebrospinal fluid (CSF) samples from patients with SSPE were quantitated by enzyme-linked immunosorbent assay by using affinity-purified measles virus proteins. Geometric mean anti-NC antibody titers were higher in the serum (6.58 +/- 0.98 [mean +/- standard deviation]) and CSF (4.38 +/- 0.74) of SSPE patients compared with controls. Anti-M antibodies were present in the serum and CSF of all SSPE samples tested but in titers lower than those of anti-NC antibodies. Geometric mean anti-M antibody titer was 3.35 +/- 0.53 in sera from patients with SSPE compared with 3.05 +/- 0.66 in sera from patients with other neurological diseases and 3.12 +/- 0.74 in sera from healthy individuals. Geometric mean anti-M antibody titer was 2.59 +/- 0.86 in the CSF of eight patients with SSPE compared with a mean less than 1.00 for patients with other neurological disease (controls). Intrathecal synthesis of anti-M or anti-NC antibodies was established in four patients with SSPE. The cellular immune responses to M, F, HA, and NC proteins were examined in four of the patients with SSPE by lymphoproliferation and were not significantly different from those in five healthy controls. The results demonstrate humoral and cellular immune responses to M protein in patients with SSPE and indicate that it is unlikely that a defect in the immune response to this virus component accounts for the disease process in the patients studied.

Measles antigen was not demonstrated in the jejunal tissue of four patients with multiple sclerosis. There was non-specific staining in cells of the lamina propria, basement membrane, and epithelial cells of the jejunum from patients with multiple sclerosis, human controls, and normal monkeys. This staining was not observed after proper absorption of reagents nor after application of Evans-blue counterstain.

In 4- and 5-month-old infants in whom the undiluted chick embryo fibroblast (CEF) Schwarz strain measles vaccine had a poor immunogenic effect, there was an increase in immunogenicity when the high sugar concentration was diminished without reference to added albumin. The human diploid cell (HDC) measles vaccine was still superior in this age group even in a lower concentration of the Ikić, Edmonston-Zagreb strain of virus. More aerosolized, HDC Ikić strain virus was required for high seroconversion rates in 4- and 5-month-old infants who had higher titers of prevaccination plaque-neutralizing (PN) antibodies. Some of these infants had a delayed immune response that was absent at six weeks but present at three months after vaccination. The data provided evidence that the PN and enzyme-linked immunosorbent assay techniques measured different antibodies that develop and persist in different ways in 4- to 5-month-old infants. The HDC lyophilized measles vaccine yielded unexpectedly high seroconversion rates after subcutaneous injection of 5,000 plaque-forming units (PFUs) in 4-, 5-, and 6-month-old infants: 69%, 89%, and 100% respectively, at 14 weeks. In 12- to 23-month-old infants there was seroconversion of 92% and 100% at six weeks after inhalation of an estimated 175 PFUs of the CEF vaccine and 375 PFUs of the HDC vaccine, respectively. Within six weeks after vaccination, the PN antibody titers were significantly higher with the CEF vaccine (geometric mean titer of 2,275) than with the HDC vaccine (geometric mean titer of 343).

The immunological responses of patients with clinical signs of SSPE were examined by the direct migration inhibition, complement-mediated antibody cytoxicity and the lymphocyte-mediated cytotoxicity assay techniques. Peripheral lymphocytes migrated similarly to controls when exposed to measles antigen. Lymphocytes from SSPE patients responded to a SSPE strain of measles infected cells in a manner similar to lymphocytes from controls. A factor which interfered with the expected activity of sensitized lymphocytes to measles virus was detected in some cerebral spinal fluid obtained from SSPE patients. The blocking activity varied from 100% in 4 of 20 patients with SSPE to no blocking in 2 of the SSPE patients. The occurrence of blocking factor in SSPE patients could not be related to sex or age of the patient, serum of CSF antibody levels, and duration of disease or outcome.

Antibody titers to measles, cytomegalovirus, and herpesviruses 1 and 2 were compared for siblings of multiple sclerosis (MS) patients sharing two, one, and no histocompatibility antigen haplotypes with the case. Significant differences were observed only for measles. Titers were significantly lower in siblings sharing no haplotypes with the case. Within case-sibling pairs, the presence of HLA-A-A3 and/or B7 affected measles antibody titers more than the presence of MS. These findings suggest that the immune response to measles in these sibships is influenced by the presence of HLA-A-A3 and/or B7 as well as another familial factor.

The CF and HI antibody titers to rubella and measles viruses, the CF titers to influenxa A, and the HI titers to parainfluenza 1, 2, and 3 were carried out on the sera of 20 patients with childhood polymyositis and their matched controls. The titers for measles, parainfluenxa 1, and influenza A were slightly higher for patients than for controls. The control group had antibody titers to rubella and parainfluenza 2 and 3 higher than or similar to those of patients. Strong patterns or significant differences for a given virus or virus group were not encountered.

Antibody to measles virus and canine distemper virus (CDV) was demonstrated in sera from patients with multiple sclerosis (MS) and from carefully matched control subjects. Elevated measles and CDV antibody titers were found in patients with MS when compared with the matched control subjects. The correlation between the measles and CDV antibody titers was quite high, suggesting that the antibody levels between the two viruses are very closely related. Based on the results of our study and a review of the literature, our conclusion is that the CDV antibody levels in patients with MS and matched control subjects are associated with occurrence of measles virus antibodies.

A new method for attaching antigens to latex by an avidin-biotin technique is described. The procedure permits control of the amount of antigen attached to the latex and eliminates the need for highly purified antigens and destructive bridging chemicals. The avidin-biotin latex agglutination assay is a simple, rapid test well suited to detection of viral antibody. The sensitivity and specificity, respectively, of the avidin-biotin latex agglutination assay compared with other assay results for antibody to viruses were as follows: cytomegalovirus, 98 and 100% (indirect hemagglutination assay); measles virus, 96 and 100% (enzyme-linked immunosorbent assay); and herpes simplex virus, 78 and 100% (indirect hemagglutination assay).

Inhalation of undiluted, aerosolized measles vaccine was immunogenic in 100% of 4- to 6-month-old and older children with and without residual maternal antibody when the human diploid cell (HDC) vaccine containing the Ikić (Edmonston-Zagreb) strain and 1% human albumin was used but in a smaller percentage of infants given a chick embryo fibroblast (CEF) vaccine, which contained the Edmonston-Schwarz strain, ten times more virus, and hypertonic sugar solution but no added protein. Prevaccination residual placentally transmitted plaque-neutralizing antibody titers of 25 to 512 that can prevent an immune response after subcutaneous injection of measles vaccine did not prevent an immune response after inhalation of aerosolized vaccine. There were no immediate clinical reactions in the 160 children who inhaled the aerosolized vaccines, and no significant subsequent reactions among the 96 children who were successfully immunized. There were no contact infections.

Measles virus was isolated in mixed cultures of lymph node cells and HeLa cells. The agent was isolated by cocultivation from biopsy specimens of two of five patients with subacute sclerosing panencephalitis. The virus was identified by hemagglutination-inhibition, immunofluorescent, and neutralization tests. Biopsies from controls did not show evidence of measles virus.