Affinity chromatography of anti-meningococcal antiserum.
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Acrylamides↗
Biomedical subjects
D L Kasper
Publications and source records attributed to D L Kasper.
Meningococcal infections. 3. Studies of group A polysaccharide vaccines.
Studies with 4 lots of group A meningococcal polysaccharides in 458 adult human volunteers showed that such vaccines are nontoxic and highly immunogenic. Comparisons of jet injection and subcutaneous (needle) methods of administration showed that both were equally immunogenic.
Antibody Formation↗
Capsular and 'O' serotype determinants of bacteroides fragilis.
Forty-one strains of Bacteroides fragilis, 20 strains of other Bacteroides species and 14 strains of other genera were examined by the indirect immunofluorescent assay (IFA) using anticapsular serum. The sixty-one Bacteroides strains were 'O' serotyped by direct agglutination tests using absorbed antisera raised against 23 strains, each with a different 'O' antigenic determinant. All 41 B. fragilis strains tested were positive by IFA with the anticapsular serum, but apart from one strain of B. distasonis, none of the remaining 19 strains of other bacteroides, i.e. B. thetaiotaomicron, B. distasonis, B. vulgatus, B. ovatus, B. melaninogenicus group and B. ureolyticus, and none of the 14 other bacterial species examined were positive. The majority of strains of saccharolytic bacteroides tested reacted with one of the 23 'O' antisera and were designated as a specific 'O' serotype; a few Bacteroides strains had multiple agglutination reactions indicating the presence of multiple antigenic determinants. All 'O' serotypes gave positive IFA tests with their homologous 'O' antisera. Common capsular determinants and 'O' antigenic determinants appear to exist on the same strains of B. fragilis. Serological typing of B. fragilis and related species would be useful in epidemiological studies.
Antigens, Bacterial↗
Virulence factors of anaerobic bacteria: an overview.
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Bacterial Infections↗
Immunochemical characterization of surface antigens of Bacteroides melaninogenicus.
Major surface antigens of Bactmbrane complex by gentle methods, purified, and characterized immunochemically. A lipopolysaccharide (LPS) was found to be chemically distinct from the LPS of facultative gram-negative bacteria in that it lacked two core sugars, 2-keto-3-deoxyoctonate and heptose, as well as beta-hydroxymyristic acid, the predominant fatty acid in the lipid A moiety. The LPS was further atypical in that it had a very low level of biologic activity. A capsular polysaccharide was demonstrated morphologically by electron microscopy with ruthenium red staining and a ferritin-labeled antibody technique. This antigen was shown to be subspecies-specific by indirect immunofluorescence. Antibody to the capsular polysaccharide was measured by an enzyme-linked immunospecific assay. The presence of a relatively impotent LPS and a surface capsular antigen may partly explain the rarity of bacteremia and septic shock due to B. melaninogenicus subspecies asaccharolyticus and the common association of this organism with abscess formation.
Animals↗
Surface antigens as virulence factors in infection with Bacteroides fragilis.
Organisms of the genus Bacteroides represent the major group of obligate anaerobes involved in human infections. Bacteroides usually cause either bacteremia or localized abscesses. Of the numerous species of Bacteroides, Bacteroides fragilis is the single most frequent clinical isolate. B. fragilis and Bacteroides melaninogenicus have chemically incomplete lipopolysaccharides as compared with the lipopolysaccharides (endotoxins) of aerobic bacteria, and the lipopolysaccharides of Bacteroides lack the biologic potency characteristic of endotoxin. This inactivity may account for the very infrequent occurrence of disseminated intravascular coagulation or purpura that can accompany sepsis due to these organisms. Furthermore, strains of B. fragilis have an immunologically common capsular polysaccharide. In an animal model of intraabdominal sepsis, the encapsulated strains caused abscesses when given without other organisms, but abscess formation from unencapsulated strains of Bacteroides generally required the administration of a synergistic aerobe. The abscesses caused by encapsulated strains were shown to be directly attributable to the capsular polysaccharide, which is an important virulence factor of this organism. Patients or experimental animals infected with B. fragilis develop antibodies to the capsular polysaccharide, and these antibodies can be detected in a radioactive antigen-binding assay.
Animals↗
Experimental animal models for anaerobic infections.
An experimental animal model that stimulates the mixed aerobic-anaerobic microflora of intraabdominal sepsis was used to study antimicrobial efficacy in vivo. Treatment of infected rats with chloramphenicol resulted in only a modest reduction in the percentage of animals surviving infection with abscesses at necropsy. This unanticipated observation led to further exploration of the predominant anaerobes associated with the experimental infection. In vitro cultures of Bacteroides fragilis, susceptible to chloramphenicol in traditional tests, were capable of reducing chloramphenicol to its aryl amine derivative, which is biologically inactive. In contrast, metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-form-associated mortality in this animal model. Subsequent studies showed that this reduction in mortality is dependent on the presence of an anaerobe and that the levels of Escherichia coli in mixed continuous culture with B. fragilis are reduced by addition of metronidazole. This reduction following addition of metronidazole was not observed either in a pure culture of E. coli or when clindamycin was added to a mixed culture. In a modification of the previously described model, infective material was placed subcutaneously into Wistar rats. Studies with this model suggested that the host's response to bacterial challenge is dependent on the site of infection and that organotropism of the implanted bacterial species is an important determinant of infection.
Abscess↗
Edward H. Kass, M.D., eulogy.
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Communicable Diseases↗
Animal model system for studying virulence of and host response to Bacteroides fragilis.
Experimental animal model systems have been used by many investigators to explore the pathogenicity of obligate anaerobes. During the last 15 years, research in our laboratory has utilized an experimental model for intraabdominal sepsis to define the contribution of obligate anaerobes to the infectious process. These studies have shown that obligate anaerobes are important components of the polymicrobic flora present during such infection. Moreover, certain anaerobes, such as Bacteroides fragilis, possess specific virulence factors, such as the capsular polysaccharide, that appear to be important to the infectious process. More recent research has used modifications of the original model system to evaluate the host immune response to B. fragilis. These studies indicate that immunization with the capsular polysaccharide provides a T cell-dependent immunity to abscess development when animals are challenged with B. fragilis. It has also been shown that the killing of B. fragilis is T cell dependent. The observations made with regard to B. fragilis in this animal model system are discussed.
Animals↗
Capsular polysaccharides and lipopolysaccharides from two strains of Bacteroides fragilis.
The capsular polysaccharide from Bacteroides fragilis strain NCTC 9343 contained six sugars: L-fucose, D-galactose, D- and L-quinovosamine, D-glucosamine, and galacturonic acid. The capsule of B. fragilis strain ATCC 23745 in addition contained D-glucose, L-fucosamine, L-rhamnosamine, and a 3-amino-3,6-dideoxyhexose, but lacked D-quinovosamine. The latter capsule also contained alanine (4%). The lipopolysaccharide of both strains contained the same sugars (L-rhamnose, D-glucose, D-galactose, and D-glucosamine) and fatty acids (13-methyltetradecanoic, 3-hydroxypentadecanoic as major constituents). The capsular polysaccharide of both strains promoted abscess formation, whereas the lipopolysaccharide failed to do so.
Abscess↗
Use of a model of intraabdominal sepsis for studies of the pathogenicity of Bacteroides fragilis.
Over the past eight years, a Wistar rat model for intraabdominal sepsis has been developed and used to document the role of obligate anaerobes in this infections. The ability of Bacteroides fragilis alone to provoke abscesses in this model system is due to a species-specific capsular polysaccharide. It has been shown that active immunization of rats with capsular polysaccharide of B. fragilis protects these animals against the development of abscesses after intraperitoneal challenge with this species. Passive transfer of hyperimmune globulin provided protection against B. fragilis bacteremia in nonimmune, challenged animals but did not confer protection against abscess development. Adoptive transfer of spleen cells from immunized to nonimmunized animals resulted in protection against abscess following challenge with B. fragilis, a finding suggesting that a T cell-dependent immune response was involved in protection. It has also been shown that inbred, congenitally athymic OLA/Rnu rats that were actively immunized developed abscesses despite the presence of capsular antibody, as did 100% of unimmunized athymic control rats. However, no phenotypically normal, littermate control rats that were actively immunized developed abscesses. These data suggest that a T cell-dependent immune response is an important part of immunity to B. fragilis. Additional experiments are being performed to better define the immunologic and chemical basis for the protection afforded by immunization.
Abscess↗
Group B streptococcal vaccines.
In recent years group B Streptococcus (GBS) has been recognized as a major perinatal pathogen. As with other encapsulated bacteria, protective immunity appears to correlate with serum antibody specific for the homologous capsular polysaccharide antigen of each serotype. Since susceptibility of the young infant to disseminated GBS infection relates to type-specific antibody deficiency in maternal serum, immunization of women with purified GBS type-specific polysaccharides has been proposed as a method for the prevention of infant disease through placental transport of protective antibodies. Candidate native polysaccharides from GBS have been purified, immunochemically and structurally characterized, and employed as immunogen in healthy adult volunteers. Native type Ia, II, and III polysaccharides have been shown to be nontoxic, safe, and immunogenic in approximately 65%, 95%, and 70%, respectively, of nonimmune adults. Antibody response to immunization approaches 100% in previously immune volunteers. Vaccine-induced type-specific antibodies to these candidate polysaccharide vaccines promote in vitro opsonophagocytosis, protect animals given a lethal challenge of homologous organisms, and are predominantly of the IgG isotype. Once similar results can be documented in women immunized during the last half of pregnancy, efficacy of these candidate GBS polysaccharide vaccines in the prevention of neonatal and young infant GBS disease should be evaluated.
Adult↗
T cell regulation of Bacteroides fragilis-induced intraabdominal abscesses.
Intraabdominal abscesses (IAA) caused by Bacteroides fragilis are a major sequela to colonic spillage into the peritoneum. The development of an animal model that closely reproduces the disease observed in humans permitted careful inspection of the cellular and/or humoral contributions to the development and control of this disease. The results obtained thus far describe an immunoregulatory T cell circuit that governs both the development of and the immunity against these abscesses. T cells of CD4+8+ phenotype induce the development of IAA in response to B. fragilis. CD8+ T cells generated in response to immunization with the B. fragilis capsular polysaccharide confer protection against the development of IAA. These cells elaborate an antigen-specific factor that mediates the observed protection by these cells. Moreover, a third type of T cell, a CD8+ cell that is also present in nonimmune individuals, is required for the immune T cell or its factor to confer protection. Thus, in the specific disease process of IAA induced by the encapsulated microorganism B. fragilis, immunity proceeds by cellular and not humoral mechanisms.
Abscess↗
Immune T cells prevent bacteroides fragilis abscesses.
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Abscess↗