Search PubMed⌕ Search

Biomedical subjects

J B Robbins

Publications and source records attributed to J B Robbins.

At least 163 records · Page 9Linked to original sources
PubMed1979

Comparative immunogenicity of vaccines prepared from capsular polysaccharides of group C Neisseria meningitidis O-acetyl-positive and O-acetyl-negative variants and Escherichia coli K92 in adult volunteers.

Three structurally and antigenically similar capsular polysaccharides, two derived from group C Neisseria meningitidis (O-acetyl-positive and O-acetyl-negative variants) and one from Escherichia coli K92, which cross-reacts with polysaccharide from group C N. meningitidis, were compared for their ability to induce anticapsular and bactericidal antibodies to group C N. meningitidis in adult volunteers. All three vaccines elicited group C-specific serum antibodies. The vaccine derived from the O-acetyl-negative variant was the most immunogenic of the three vaccines. With use of radiolabeled O-acetyl-positive group C N. meningitidis polysaccharide antigen, the geometric mean titers of antibody in serum were 41.7 microgram/ml to the O-acetyl-negative variant, 22.8 microgram/ml to the O-acetyl-positive variant, and 7.1 microgram/ml to E. coli K92. Antibodies induced by all three vaccines were bactericidal for both of the group C N. meningitidis polysaccharide variants. An inverse relation between the comparative immunogenicity of the O-acetyl-negative polysaccharide and the virulence of group C N. meningitidis was found.

Adult↗
PubMed1979

Comparative immunogenicity of group 6 pneumococcal type 6A(6) and type 6B(26) capsular polysaccharides.

The comparative immunogenicity of the two cross-reacting group 6 pneumococcal capsular polysaccharides, type 6A(6) and type 6B(26), was studied with hyperimmune rabbit typing antisera and with sera from adult volunteers injected with polyvalent pneumococcal vaccines containing either 50 mug of type 6A (U.S. designation, type 6) or 50 mug each of type 6A and type 6B (U.S. designation, type 26) polysaccharides. Both group 6 polysaccharides were linear copolymers composed of 1 mol each of d-galactose, d-glucose, l-rhamnose, and d-ribitol phosphate. They differed only in that type 6A had a rhammopyranosyl-(1 --> 3)-d-ribitol bond and the type 6B had a rhamnopyranosyl-(1 --> 4)-d-ribitol bond. Quantitative precipitation and absorption analyses with rabbit hyperimmune antisera induced by simultaneous injection with type 6A and type 6B organisms revealed extensive cross-reactions between the two group 6 polysaccharides. There was less, although still quite extensive, cross-reactivity between the two group 6 polysaccharides examined with antisera from rabbits injected with only one of the group 6 pneumococci. In a radioimmunoassay, using (14)C internally labeled type 6A or type 6B polysaccharide antigens, there was no difference in the serum antibody level to either type of volunteer injected with polyvalent pneumococcal vaccines containing type 6A or both type 6A and type 6B polysaccharides. These studies indicate that the structural similarity of the pneumococcal group 6 polysaccharides confers extensive cross-reactivity with hyperimmune typing antisera prepared with whole organisms or after injection of purified polysaccharides in adult volunteers. With our current polysaccharides, it appears that a polyvalent pneumococcal vaccine formulation that contains only type 6A will serve to induce the maximum amount of serum antibodies to both group 6 organisms.

Adult↗
PubMed1978

Association between cross-reacting Escherichia coli K100 and disease caused by Haemophilus influenzae type b.

An unexpected association between Haemophilus influenzae type b (HIB) disease and simultaneous intestinal colonization with cross-reacting Escherichia coli K100 strains is reported. E. coli K100 were found in 18 of 92 (19.5%) HIB patients, compared with 2.5% in healthy individuals of comparable age and in none of 21 patients with meningitis caused by other bacteria. There was no difference in disease outcome, serum antibodies, and circulating HIB antigen between the E. coli K100-positive and -negative HIB patients. Possible explanations and implications of this association are discussed.

Antibodies, Bacterial↗
PubMed1978

Characterization of the cross-reaction between type 19F(19) and 19A(57) pneumococcal capsular polysaccharides: compositional analysis and immunological relation determined with rabbit typing antisera.

The immunological relation, physicochemical characteristics, and chemical composition of type 19F(19) and 19A(57) within the cross-reactive group 19 pneumococcal capsular polysaccharides were studied. By using rabbit hyperimmune diagnostic antisera in agglutination, immunodiffusion, quantitative precipitation, and absorption assays, extensive cross-antigenicity and cross-immunogenicity were demonstrable between the disease-associated types 19F(19) and 19A(57). Types 19B(58) and 19C(59), rarely associated with human disease, were extensively cross-reactive with each other but reacted weakly with types 19F(19) and 19A(57). Both types 19F(19) and 19A(57) polysaccharides contained trace amounts of protein and nucleic acid and had comparable molecular sizes as determined by gel filtration. Compositional analysis showed type 19F(19) to contain rhamnose, glucose, N-acetylmannosamine, and a phosphate ester. Type 19A(57) contained these four moieties, and in addition, contained fucose, galactose, and N-acetylglucosamine. Plans for using this information to evaluate current and proposed formulation of multivalent pneumococcal polysaccharide vaccines are discussed.

Antigens, Bacterial↗
PubMed1978

Cell-free biosynthesis of the O-acetylated N-acetylneuraminic acid capsular polysaccharide of group C meningococci.

A cell-free system was established to study the biosynthesis of group C meningococcal capsular polysaccharide, an alpha-2 leads to 9-linked N-acetylneuraminic acid (NeuAc) homopolymer containing O-acetyl groups at either C7 or C8. Sialyltransferase activity, isolated from group C meningococcus strain C-11, catalyzed incorporation of [14C]NeuAc from CMP (CMP--[14C]NeuAc) into polymeric form. This sialyltransferase was stimulated by addition of meningococcus group C and Escherichia coli K92 capsular polysaccharides, the latter being an alpha-2 leads to 8- and alpha-2 leads to 9-linked NeuAc heteropolymer. Group C meningococcal sialyltransferase did not require divalent ions but was stimulated by Mn2+. Attempts to demonstrate a lipid-soluble intermediate in the biosynthesis of this NeuAc polymer were unsuccessful. Meningococcal group C sialyltransferase incorporated NeuAc into a membrane-associated product. The polysaccharide can be extracted from the membrane-bound fraction with Triton X-100. The newly synthesized polysaccharide coprecipitates with authentic group C antigen in meningococcal group C antiserum and is degraded by sodium metaperiodate, indicating that the NeuAc polymer synthesized by the cell-free system consists of alpha-2 leads to 9 linkage. Meningococcal group C spheroplast membranes contain an O-acetylase that can catalyze the transfer of acetyl groups from acetyl coenzyme A to the in vitro-synthesized polysaccharide.

Acetylation↗
PubMed1978

Serogroup identification of Neisseria meningitidis: comparison of an antiserum agar method with bacterial slide agglutination.

A serum agar method for serogrouping Neisseria meningitidis is described and compared with conventional bacterial slide agglutination. There was 93% agreement for 300 strains examined individually by each method. Among strains from serogroups A, B, C, Y, and W135, there was 100% correlation, whereas strains from serogroup 29E (Z') had only 67% correlation. The serum agar method was rapid, as well as easy to perform and interpret. The potential benefits of this method for epidemiological studies and reference laboratories processing large numbers of meningococcal isolates are emphasized.

Agglutination Tests↗
PubMed1978

Characterization and mitogenic activity of Haemophilus influenzae type B capsular polysaccharide.

Studies were conducted on the characterization of Haemophilus influenzae type b polysaccharide (HITB-PS) and its mitogenic activity upon peripheral lymphocytes. This capsular polysaccharide was found to contain hexosamines and hexoses in addition to the main components of ribose and ribitol phosphate. The molecular weight of HITB-PS was determined as 585,000. The affinity constant of HITB-PS to unfractionated lymphocytes was 3.13 X 10(3) M-1 with 1.11 X 10(4) binding sites per cell. HITB-PS was found to be mitogenic for both human T and B lymphocytes. At optimum doses, a three to five fold increase in 3H-thymidine incorporation into T and B cells was observed. Higher than optimum doses resulted in suppression of this mitogenicity. The effect of concanavalin A (Con A) mitogenicity was detected in T and B cells treated with effective as well as suppressive doses of HITB-PS; the mitogenic activities of Con A and HITB-PS were found to be independent of each other.

B-Lymphocytes↗
PubMed1978

Prospects for the prevention of bacterial meningitis with polysaccharide vaccines.

MOST SUPPURATIVE INFECTIONS OF THE MENINGES ARE CAUSED BY FIVE BACTERIAL SPECIES: Escherichia coli, Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis, and group B streptococcus. The immune response of adults to pneumococcal capsular polysaccharides has been studied in great detail and their responses to meningococcal and H. influenzae type b capsular polysaccharides are quite similar. Immune responses of adults to E. coli and group B streptococcal antigens are disappointing. The responses of children below the age of 7 years differ both quantitatively and in duration. Early experience shows that useful antibody titres can be achieved with certain antigens but further studies are required. In order to prevent bacterial meningitis by immunization, three vaccine formulations will need to be developed. When epidemic meningococcal disease occurs in a population, the vaccine containing only components of the meningococcus would be applied to a large segment of the population to terminate the epidemic. The second vaccine would contain components of H. influenzae type b, pneumococcus, and the meningococcus and would be administered in the first year of life, and repeated at suitable intervals to maintain life-long immunity. The third vaccine, designed to prevent neonatal meningitis caused by E. coli K1 and group B streptococci, would be administered to women preferably during the third trimester of pregnancy, so that their offspring would inherit sufficient antibodies to protect them during the first 3 months of life.The vaccine against the meningococcus is a reality and has been used extensively during major epidemics, with excellent results. The two vaccines for control of endemic bacterial meningitides do not exist as yet, but the prospects are good.

Adult↗
PubMed1978

The regulation of the immune response of mice to Haemophilus influenzae type b capsular polysaccharide.

The regulation of age-related antibody response to Haemophilus influenzae type b polysaccharide (HITB-PS) was studied by measuring the splenic plaque forming cells (PFC) following immunization with this capsular polysaccharide. The magnitude of PFC response to HITB-PS was found to be dose-related, enhanced by Freund's complete adjuvant and influenced by the genetic strain of mice. Priming with a low dose of HITB-PS did not induce a state of immunological unresponsiveness. Treatment with antilymphocyte serum significantly increased the PFC response to HITB-PS. Athymic nude mice showed an enhanced ability to induce both IgG and IgA-PFC responses as well as a significant increase in the biosynthesis of protein and mitogenicity in spleen cells. These findings suggest that the immune response to HITB-PS is regulated by the suppressor T cell. The magnitude of the IgM-PFC response induced by HITB-PS in mice increased gradually from two weeks of age and reached a plateau at 8 weeks. Treatment with fetuin resulted in the inhibition of direct IgM and IgG-PFC responses to HITB-PS; the suppressive effect on the immune response was more profound and lasting in young than in adult mice.

Age Factors↗
PubMed1977

Structural studies on the sialic acid polysaccharide antigen of Escherichia coli strain Bos-12.

A polysaccharide, antigenically related to group C meningococcus, has been isolated from Escherichia coli strain Bos-12 (016; K92; NM). Like groups B and C meningococcal polysaccharide, the Bos-12 antigen is a pure polymer of sialic acid. 13C NMR studies on the meningococcal group B and C polysaccharides have indicated that the former consists of sialic acid units linked 2 leads to 8- alpha, whereas the latter contains the sialic acid residues linked 2 leads to 9-alpha (Bhattacharjee, A.K., Jennings, H.J., Kenny, C.P., Martin, A., and Smith, I.C.P. (1975), J. Biol. Chem. 250, 1926). Comparison of natural abundance 13C NMR spectra of the Bos-12 polysaccharide with group B and C meningococcal polysaccharides established that Bos-12 was either (a) an equimolar mixture of 2 leads to 8-alpha linked sialic acid homopolymers or (b) a 2 leads to 8-alpha/2 leads to 9-alpha heteropolymer. These possibilities were distinguished in the following manner. The fact that Bos-12 polysaccharide precipitated with anti-group C serum but not with anti-group B serum would seem to exclude a. Further, chemical studies (periodate oxidation followed by tritiated NaBH4 reduction) gave saccharides with a radioactive-labeling pattern expected for alternating 2 leads to 8-alpha/2 leads to 9-alpha sialic acid linkages. Bos-12 is thus an 2 leads to 8/2 lead to 9-alpha heteropolymer.

Borohydrides↗
PubMed1977

Frequency of E. coli K antigens in urinary-tract infections in children.

The somatic (O) and casular (K) antigens of Escherichia coli from the urine of patients with acute pyelonephritis, acute cystitis, and asymptomatic bacteriuria, and in the faeces of healthy schoolchildren have been investigated. Typing antisera for sixteen capsular acidic polysaccharide K antigens were used, and five (numbers 1, 2, 3, 12, and 13) accounted for 70% of isolates from patients with acute pyelonephritis. These five K antigens were found to a lesser extent in the three other study groups. Thus, only a few K polysaccharides are associated with virulent properties of E. coli for the upper urinary tract. This finding is similar to the association of only some capsular types of pneumococci, meningococci, and Haemophilus influenzae with invasiveness. The identification of virulence markers for E. coli associated with upper-urinary-tract disease may permit more successful control with reference to preventive immunisation.

Acute Disease↗