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Biomedical subjects

M A Mufson

Publications and source records attributed to M A Mufson.

At least 55 records · Page 3Linked to original sources
PubMed1987

Pneumococcal antibody levels one decade after immunization of healthy adults.

The authors investigated the persistence of anticapsular pneumococcal antibodies in 21 subjects one decade after administration of a single dose of a polyvalent pneumococcal polysaccharide vaccine. Fourteen vaccinees received a hexavalent vaccine composed of the polysaccharides of capsular types 1, 3, 4, 7F, 8, and 12F; four vaccinees received an octavalent vaccine consisting of these six polysaccharides and also those of capsular types 14 and 19F; and three vaccinees received a nonavalent vaccine that also included type 5 capsular polysaccharide. Antibody was measured by radioimmunoassay. The authors detected persistently elevated anticapsular antibody levels among more than one half of vaccinees who developed a significant rise in antibody 1 month following immunization one decade after administration of pneumococcal polysaccharide vaccine when these levels were compared to prevaccine levels for pneumococcal capsular types 4, 7F, and 8. This finding was not the case with pneumococcal types 1, 3, 12F, 14, and 19F; less than two fifths of vaccinees maintained increased levels of anticapsular antibody to these types one decade after administration of pneumococcal vaccine. Geometric mean anticapsular antibody levels for types 7F and 8 only were significantly higher one decade after vaccine administration compared with the levels before immunization (t-test, p less than 0.01).

Adult↗
PubMed1987

Preparation and characterization of monoclonal antibodies directed against five structural components of human respiratory syncytial virus subgroup B.

Mouse hybridomas producing antibodies against the structural proteins of strain WV4843, a subgroup B strain of respiratory syncytial (RS) virus, were produced by fusion of Sp2/0 myeloma cells with spleen cells from BALB/c mice immunized with purified preparations of the virus. After immunoprecipitation test with [35S]methionine-labelled extracellular virions, 35 clones found to produce antibodies against the fusion (F) protein, six against the member (M) protein, 21 against the nucleocapsid (NP) and eight against the phospho- (P) protein were further characterized. Immunoprecipitation with [3H]glucosamine-labelled intracellular virus polypeptides detected nine hybridoma cell lines producing antibodies against the large glyco- (G) protein of the virus. By competitive binding ELISA tests with monoclonal antibodies against each of the structural components, a minimum of two, 24, four, 15 and three epitopes were detected on the G, F, M, NP and P proteins, respectively. Eleven monoclonal antibodies directed against nine epitopes of the F protein could neutralize the infectivity of the virus. In contrast, none of the nine monoclonal antibodies against G could neutralize the infectivity of the virus. In order to find out more about the antigenic relationship between human and bovine RS virus strains all monoclonal antibodies were reacted with subgroup A RS virus and also with three different strains of bovine RS virus and one strain of caprine RS virus in immunofluorescence, ELISA and immunoprecipitation tests. In addition, 31 previously developed monoclonal antibodies against subgroup A virus were reacted with the bovine and caprine strains. The numbers of monoclonal antibodies of subgroup B specific for the B type of the two human subgroups were 9/9, 3/35, 0/6, 0/21, 0/8, for the G, F, M, NP and P proteins, respectively. No antigenic variations were found between the three bovine strains and the caprine strain. They did not react with the nine monoclonal antibodies against the G protein of subgroup B, nor did they react with nine monoclonal antibodies against subgroup A. Most but not all of the monoclonal antibodies against the other structural proteins of the two human RS virus subgroups reacted with the four strains. All 11 monoclonal antibodies against the F protein of subgroup B that could neutralize the infectivity of subgroup B also reacted with the bovine strains and neutralized their infectivity. It is concluded that although the bovine strains share many epitopes with the two human subgroups, they are antigenically distinct from the human viruses.

Antibodies, Monoclonal↗
PubMed1987

Subgroup characteristics of respiratory syncytial virus strains recovered from children with two consecutive infections.

Respiratory syncytial virus strains from 13 children who had repeat infections at least 1 year apart were identified as either subgroup A or subgroup B according to reaction patterns with several monoclonal antibodies directed against the large surface glycoprotein (G), fusion protein (F), nucleoprotein (NP), and matrix protein (M). The virus strains were characterized by enzyme immunoassay, polyacrylamide gel electrophoresis, and immunofluorescence procedures. During the first infection, 10 children had subgroup A strains and 3 had subgroup B strains. Of the 10 children with subgroup A strains during their first infection, 6 had subgroup B and 4 had subgroup A strains during the second infection. Of the three children with subgroup B strains during their first infection, one had subgroup A and two had subgroup B strains during their second infection. No child experienced unusually severe respiratory tract illnesses during second infections with respiratory syncytial virus. Fourfold or greater rises in serum antibody as determined by enzyme immunoassay were as common after the first infection as after the second infection among the seven children tested. Thus, second infections with strains of either subgroup of respiratory syncytial virus did not potentiate respiratory illness, and infection with subgroup A strains of respiratory syncytial virus provided some protection from a second infection with the homologous, but not the heterologous, subgroup of the virus.

Acute Disease↗
PubMed1986

Detection of antigen in immune precipitates by silver staining of SDS-polyacrylamide gels.

The silver staining technique of Merril et al. (1981) was used to identify antigens separated by SDS-PAGE after dissociation of immune complexes purified by absorption with staphylococcus A protein. The five and four dominating structural components of measles and RS virus (Mr range 28,000 to 79,000) respectively precipitated with monoclonal antibodies were readily identified, except when the Mr of the virus-specific antigen was in the same range as immunoglobulin heavy and light chains. Specific antigens were identified less effectively after precipitation with polyclonal sera because of a larger background of stainable proteins. This method, which combines the sensitivity and high resolution of silver staining and the specificity of immune complexing with monoclonal antibodies, is rapid and inexpensive.

Antibodies, Monoclonal↗
PubMed1986

Structural differences between subtype A and B strains of respiratory syncytial virus.

Differences in the properties of homologous intracellular structural components of eight strains of subtype A and eight strains of subtype B of human respiratory syncytial (RS) virus were examined. The size of the fusion (F) protein cleavage products and the phosphoprotein (P) showed systematic differences between virus strains representing the two subtypes. The apparent mol. wt. in SDS-polyacrylamide gels under reducing conditions was 48,000 (48K) and 46K to 47K for the cleavage product F1 in subtype A and B strains, respectively. The size of the F2 protein was 18K to 20K. The subtype B strains showed a slightly higher mol. wt. of this protein compared to the subtype A strains. The size of the P protein was 36K in subtype A strains, but only 34K in subtype B strains. Variations also occurred in the size of the glycoprotein (G) and the 22K to 24K structural protein. These variations did not correlate with the virus subtypes, but were strain-specific. The size of non-glycosylated forms of the F protein cleavage products was determined by use of material from tunicamycin-treated cells. A 44K to 45K non-glycosylated form of the F1 protein was detected with subtype A virus strains, but the corresponding protein of subtype B strains was not reproducibly identified, presumably due to instability in the absence of glycosylation or altered antigenicity. Monoclonal antibody immunosorbent-bound viral glycoproteins were partially digested with proteases. The pattern of breakdown products of the F1 protein was distinctly different between subtype A and B strains, but it was similar among strains of the same subtype. No subtype-specific pattern was seen in proteolytic digests of monoclonal antibody-bound G protein.

Electrophoresis, Polyacrylamide Gel↗
PubMed1985

Two distinct subtypes of human respiratory syncytial virus.

Antigenic variation of human respiratory syncytial (RS) virus strains was analysed using a collection of nine, six, six, nine and one monoclonal antibodies respectively directed against the large glycoprotein (G), fusion protein (F), matrix protein (M), nucleoprotein (NP) and phosphoprotein (P) components of the Long strain of RS virus. A comparison was made with seven other strains isolated during different years in radioimmune precipitation analyses and immune fluorescence tests. Two different subtypes of the virus were demonstrable. Subtype A included the prototype strains Long and A2 and virus isolates from 1973, 1983 and 1984; subtype B included four virus strains isolated in successive years from 1979 to 1982. Subtype A viruses reacted with all the antibodies, whereas subtype B viruses showed different epitope characteristics in four structural components. The number of altered epitopes were 5/6, 1/2, 2/6 and 1/6 in the G, F, M and NP components, respectively. It is concluded that the two subtypes have evolved separately. The finding of two subtypes may explain previously observed strain variations in neutralization tests, and gives a new perspective on the immunobiology of RS virus.

Antibodies, Monoclonal↗
PubMed1984

Reactivity and antibody responses of volunteers given two or three doses of pneumococcal vaccine.

Pneumococcal antibody responses and adverse reactions were assessed in 12 healthy volunteers who received either two (10 volunteers) or three (2 volunteers) doses of pneumococcal polysaccharide vaccines at 1 or 2 year intervals. The volunteers were given hexavalent (types 1, 3, 4, 7F, 8, 12F) octavalent (types 14, 19F added) nonavalent (type 5 added), and tridecavalent (types 6A, 6B, 9N, 18C, 23F added; type 5 removed) pneumococcal vaccines. Local and systemic reactions following any of the vaccines, either first, second, or third doses, were low, and these were mild; fever did not occur. Twelve volunteers received types 1, 3, 4, 7F, 8, and 12F in two doses of vaccine, and four volunteers received types 14 and 19F in two doses of vaccine. Primary immunization induced significant antibody rises to these antigens in most volunteers, but a second dose of vaccine did not further increase antibody levels to the same antigens; when it also contained new antigens, antibody rises usually developed to these antigens. Although the data are limited to detailed studies of only 12 persons, the results suggest that additional studies of this issue would seem appropriate.

Adult↗
PubMed1983

Impact of viral respiratory diseases on infants and young children in a rural and urban area of southern West Virginia.

Acute viral respiratory disease occurring in children residing in the community of Huntington, West Virginia (urban children) or in the hollows surrounding Huntington (rural children) was evaluated from September 1978 through March 1980. Cohorts of ambulatory children residing in each area were studied for the occurrence of mild to moderate respiratory disease. All children admitted to hospitals were evaluated for the occurrence of severe viral respiratory disease. Respiratory secretions were obtained from children for isolation of viruses. Epidemics of illnesses occurred simultaneously in the urban and rural groups of children. Among both the urban and rural ambulatory children, adenoviruses were the most common viruses isolated, and respiratory syncytial virus was the second most common viral pathogen isolated. Among the urban and rural hospitalized children, respiratory syncytial virus was the most common virus isolated. The distribution of the diagnoses, pneumonia, bronchiolitis, or croup, was similar among the urban and rural children who required hospitalization. The risk of hospitalization because of respiratory disease was found to be one in every 20 children during the first four years of life, and the estimated risk of hospitalization because of respiratory syncytial virus infection was one in 30. No differences were detected in the incidence of severe viral respiratory disease among children residing in urban or rural areas in southern West Virginia.

Child, Preschool↗
PubMed1983

Long-term persistence of antibody following immunization with pneumococcal polysaccharide vaccine.

Thirty-seven healthy volunteers who received a pneumococcal polysaccharide vaccine were tested 4, 5, or 6 years after immunization for circulating type-specific pneumococcal antibody by radioimmunoassay of their sera. Each volunteer was immunized with one of four different pneumococcal vaccines containing 50 micrograms of each of 6, 8, 9, or 13 capsular polysaccharides; a few volunteers received octavalent or tridecavalent pneumococcal vaccines combined with bivalent influenza virus vaccine in a single syringe. Four years after immunization, the mean antibody level was 90% of the level achieved 4 weeks after vaccination. Among volunteers tested 5 years after immunization (including three 6 years after vaccination), the mean antibody level was 76% of that 4 weeks after inoculation. These findings confirm the long-term persistence of vaccine-induced type-specific pneumococcal antibodies and suggest that the interval between repeated doses of pneumococcal vaccine should be at least 5 years.

Adult↗
PubMed1982

Pneumococcal disease in a medium-sized community in the United States.

To assess the importance of bacteremic pneumococcal disease among the population of one "average" American community, we studied all hospitalized patients who had Streptococcus pneumoniae isolated from blood, CSF, pleural fluid, or ascitic fluid during the years 1978 through 1981 in Huntington, WVa, and environs. Seventeen patients were children younger than 13 years, and 71 were adults. The case fatality rate from bacteremic pneumococcal disease among adults was 30%, and among children it was 6%. It was much higher (88%) in adults older than 50 years with extrapulmonary disease. Approximately four fifths of the typed isolates from adults or children were types included in the current vaccine. Eighty-nine percent of the adults who died of pneumococcal infection had been candidates for pneumococcal vaccine, but only one patient had received vaccine, just before becoming ill with pneumococcal disease. These data provide a basis for widespread use of pneumococcal vaccine in high-risk groups.

Adolescent↗
PubMed1982

Parenteral administration of live respiratory syncytial virus vaccine: results of a field trial.

A live respiratory syncytial virus (RSV) vaccine administered parenterally was evaluated for efficacy in a double-blind, placebo-controlled field trial in 510 children six to 47 months of age. Among the 233 recipients of live RSV vaccine, 68 of 98 initially seronegative children (as determined by enzyme-linked immunosorbent assay) developed antibody to RSV; 25 of the 30 initially seronegative children who did not develop antibody were less than 12 months old, which suggested that very low levels of maternal antibody (undetectable by enzyme-linked immunosorbent assay) inhibited replication of the vaccine virus. The children were monitored for the occurrence of naturally acquired RSV infection in two RSV epidemics, and there was no difference in the frequency of upper or lower respiratory tract disease caused by RSV between the live RSV vaccine recipients who developed vaccine-induced antibody and the placebo vaccine recipients. Thus, this live RSV vaccine administered parenterally was not efficacious.

Antibodies, Viral↗
PubMed1982

Comparison of enzyme-linked immunosorbent assay and neutralization techniques for measurement of antibody to respiratory syncytial virus: implications for parenteral immunization with live virus vaccine.

The sensitivity of an enzyme-linked immunosorbent assay (ELISA) to detect low levels of antibody to respiratory syncytial (RS) virus was compared with a tube dilution neutralization test (NEUT) on sera obtained from children who received a parenteral live RS virus vaccine. Among the children who developed antibody in response to live RS virus vaccine. ELISA was as sensitive as NEUT at detecting antibody increases. Some children who did not have detectable prevaccine ELISA antibody possessed NEUT antibody; these children were generally less than 12 months old, suggesting that they had low levels of maternal antibody. Low levels of NEUT or ELISA antibody were associated with the absence of antibody increases after injection of live RS virus vaccine. The quantity of antibody stimulated by this live RS virus vaccine was small compared with that which was stimulated by naturally acquired RS virus infection. We concluded that ELISA is a satisfactory test for determining antibody to RS virus in vaccine field trials, given the understanding that low levels of preexisting antibody are not detected in some instances.

Antibodies, Viral↗