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K Redhead

Publications and source records attributed to K Redhead.

33 records · Page 2Linked to original sources

Persistence of antibody after accelerated immunisation with diphtheria/tetanus/pertussis vaccine.

OBJECTIVE: To determine the persistence of antibody to diphtheria, tetanus, and pertussis in children receiving an accelerated schedule of primary immunisation. DESIGN: Controlled study of antibody testing of blood samples from children immunised according to various schedules: three doses of triple vaccine completed at 8-13 calendar months, 6-7 calendar months, before 6 calendar months, or three doses followed by diphtheria/tetanus before age 2. SETTING: Plymouth Health Authority. SUBJECTS: 129 children aged 4 years who had received three doses of diphtheria/tetanus/pertussis vaccine with or without a diphtheria/tetanus booster. MAIN OUTCOME MEASURES: Diphtheria and tetanus antitoxin concentrations and antibody titres to pertussis toxin, filamentous haemagglutinin, and agglutinogens 2 and 3. RESULTS: All children had protective concentrations of antitoxin to diphtheria and tetanus (greater than or equal to 0.01 IU/ml). There was no evidence of a significant difference in diphtheria or tetanus antitoxin concentrations and pertussis antibody titres in children immunised with an accelerated course (third dose of triple vaccine before 6 months) compared with those who received a longer course (third dose at 8-13 months) with no booster (geometric mean antitoxin concentration 0.411 (95% confidence interval 0.273 to 0.618) v 0.426 (0.294 to 0.616) for diphtheria and 0.358 (0.231 to 0.556) v 0.299 (0.197 to 0.453) for tetanus; geometric mean antibody titres 903 (500 to 1631) v 1386 (848 to 2266) for pertussis filamentous haemagglutinin, 179 (130 to 248) v 232 (167 to 322) for pertussis toxin, and 2002 (1276 to 3142) v 3591 (2220 to 5809) for agglutinogens 2 and 3). CONCLUSION: Immunisation with three doses of triple vaccine at monthly intervals completed before 6 months of age probably provides adequate protection against diphtheria, tetanus, and whooping cough which will persist until the age of the preschool booster.

Antibodies, Bacterial↗

Variability in LPS composition, antigenicity and reactogenicity of phase variants of Bordetella pertussis.

Comparison of lipopolysaccharides (LPS) from phase variants of different strains of Bordetella phase variants of different strains of Bordetella pertussis has shown a difference in their composition, antigenicity and reactogenicity. Phase I variants of B. pertussis, with the exception of strain 134, contain a preponderance of LPS I whereas the major component of LPS of phase IV variants is LPS II. Sera raised to LPSs of phase I strains, other than 134, cross-react with each other but not with phase IV LPSs; and similarly all sera raised to phase IV LPSs cross-react with each other and with LPS from 134 phase I. The LPSs of all phase I variants, including that of 134, are approximately ten-fold or more reactive in the limulus amoebocyte lysate assay (LAL) than phase IV LPSs. In the human mononuclear cell pyrogen assay phase IV LPSs also stimulated a lower response than phase I LPSs. The B. pertussis phase I LPSs are 10-times more reactive than Escherichia coli standard endotoxin in the LAL assay but 100-times less reactive than E. coli LPS in the monocyte test for pyrogen. The SDS-PAGE profiles of B. pertussis LPSs are quite different from those of B. parapertussis and B. bronchiseptica strains. B. pertussis LPSs produced a typical lipo-oligosaccharide (LOS) pattern. B. bronchiseptica LPS produced a similar pattern but was antigenically distinct from B. pertussis LPSs I and II. B. parapertussis in contrast produced a ladder pattern typical of smooth type LPS.

Animals↗

Acquisition of iron from transferrin by Bordetella pertussis.

It has been demonstrated that under iron-restricted conditions Bordetella pertussis can take up iron from human transferrin within 30 min of exposure. B. pertussis utilizes two mechanisms for acquiring iron from human transferrin, a direct contact method and a siderophore mediated system. Both systems are shown to result in bacterial internalization of iron from transferrin. However, direct contact between B. pertussis and transferrin provides far more effective iron uptake than siderophore activity alone.

Biological Transport↗

A collaborative assay of the proposed third British Reference Preparation for Pertussis Vaccine and of the relative potencies of the second International Standard and the second British Reference Preparation for Pertussis Vaccine.

A collaborative assay has been carried out to estimate the mouse protective potency of a freeze-dried preparation of Bordetella pertussis (88/522) intended to serve as the third British Reference Preparation for Pertussis Vaccine (third BRP). The opportunity was also taken of reassessing the relationship between the second International Standard for Pertussis Vaccine and the second British Reference Preparation for Pertussis Vaccine (second BRP). Workers in nine laboratories took part in the study and together completed 19 assays which were considered to be statistically valid. Based on the results of the study it is proposed that ampouled preparation code number 88/522 be established as the third BRP with an assigned potency of 50 IU per ampoule. The evidence of this study also suggests that the relationship between the second International Standard for Pertussis Vaccine and the second BRP has not changed significantly since they were originally established.

Animals↗

Antimicrobial effect of human milk on Bordetella pertussis.

It has been demonstrated that human milk, unlike bovine milk, can reduce the viability of Bordetella pertussis. This antibacterial activity was not due to the presence of antibiotics or antibodies in the human milk. Reducing the level of available iron or increasing the concentration of lysozyme in bovine milk did not induce anti-B. pertussis activity. Analysis of total fatty acids revealed that human milk contained significantly more linoleic acid than bovine milk. However, the addition of linoleic acid to bovine milk did not inhibit the growth of B. pertussis.

Animals↗

Human serum antibody responses to Bordetella pertussis infection and pertussis vaccination.

We used an immunoblotting technique to compare the serum antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), a 69-kilodalton (kDa) adenylate cyclase-associated protein (69 KD protein), and Bordetella pertussis outer membrane proteins (OMPs) following either B. pertussis infection or immunization with whole-cell pertussis vaccine. Infection and vaccination induced nearly equally intense antibody responses to PT and to FHA, but vaccination induced stronger antibody responses to the 69 KD protein and to many OMPs. The importance of serum antibody responses to the 69 KD protein and to B. pertussis OMPs other than PT and FHA in conferring immunity to pertussis after vaccination is unknown. Serum antibody responses to PT following either infection or vaccination were almost exclusively to the 28-kDa enzymatic subunit (S1) and only rarely and weakly to the lesser molecular weight binding subunits (S2-S5).

Adenylate Cyclase Toxin↗

Human cellular immune responses to Bordetella pertussis infection.

We have compared the responses of peripheral blood leucocytes from three groups (i) patients suffering from pertussis (whooping cough), (ii) clinical staff caring for those patients and laboratory staff working with Bordetella pertussis, and (iii) staff with no known recent contact with B. pertussis. In vitro stimulation with filamentous haemagglutinin (FHA) caused significant increases in proliferation of only the patient group's lymphocytes. In vitro stimulation with pertussis toxin (PT) caused a large increase in proliferation of lymphocytes from all three groups and in the patient group the increase in proliferation was related to the dose of PT. Interleukin 2 (IL-2) production by leucocytes from all three groups was significantly increased following challenge with FHA or PT. The increases in IL-2 production were greatest in lymphocytes from patients with pertussis. Challenge with toxoided pertussis toxin had no effect on either proliferation or IL-2 production in any of the groups.

Adolescent↗

The activity of purified Bordetella pertussis components in murine encephalopathy.

A murine encephalopathic syndrome can be induced by the administration of BSA and whole-cell pertussis vaccine. The present paper reports studies of the capacity of purified individual pertussis components to induce this effect. Pertussis toxin and endotoxin together with a highly immunogenic sensitizer protein were required to induce the effect. The strength of the antibody response to the sensitizer appeared to be more important than the H-2 type of the recipient in determining the susceptibility of different mouse strains. The relevance of this syndrome to the study of possible vaccine-induced encephalopathy in man is uncertain and requires further investigation.

Animals↗

Interaction of lactoferrin and transferrins with the outer membrane of Bordetella pertussis.

Bordetella pertussis was able to grow in vitro under conditions where the only iron present was bound to the iron-binding proteins ovotransferrin, transferrin or lactoferrin. Under these conditions the bacteria produced neither hydroxamate nor phenolate-catecholate siderophores to assist in the procurement of iron. Examination of B. pertussis outer-membrane preparations by SDS-PAGE and immunoblotting showed that the iron-binding protein ovotransferrin was bound directly to the bacterial surface. Assays of the binding of radiolabelled transferrin by the bacteria showed that the association was a specific process and that there was turnover of the bound proteins. Competitive binding assays indicated that lactoferrin could be bound in the same way. It is suggested that B. pertussis obtains iron directly from host iron-binding proteins during infection.

Bacterial Outer Membrane Proteins↗

The primary and secondary cellular immune responses to whole cell Bordetella pertussis vaccine and its components.

The cellular immune responses of Balb/c mice and Wistar rats immunized in hind footpads with intact killed Bordetella pertussis were found to differ from those of similar animals immunized with other bacteria including Bordetella bronchiseptica, Salmonella typhimurium and Escherichia coli. All the bacteria stimulated increases in cell number, proliferation and interleukin 2 (IL-2) production in popliteal lymph nodes which peaked 3-5 days after injection and decreased to resting levels by day 7. However, B. pertussis also caused a second peak in all three parameters at 11 days after immunization. This peak was not seen following injection with any of the other bacteria. Bordetella pertussis also caused systemic effects, increased cellular proliferation in bone marrow and thymus, with similar biphasic kinetics. It possesses a potent toxin, distinguishing it from the closely related B. bronchiseptica. The use of purified materials confirmed that the presence of this pertussis toxin (PT) was responsible for the later peak in stimulation, whereas lipopolysaccharide (LPS) in combination with PT and also the filamentous haemagglutinin (FHA) could mimic the early peak of stimulation. Primary immunization with B. pertussis was also shown to generate lymph node cells which responded in vitro to secondary challenge with B. pertussis cells, FHA or PT. Both proliferation and IL-2 production were enhanced, except with FHA which only increased IL-2 production. Lymph node cells from mice immunized with E. coli showed no such responses.

Animals↗

The effects of purified components of Bordetella pertussis in the weight gain test for the toxicity testing of pertussis vaccines.

The effects of highly purified preparations of three Bordetella pertussis components--pertussis toxin (PT), lipopolysaccharide (LPS) and filamentous haemagglutinin (FHA)--were examined in the mouse weight gain test, a toxicity test for pertussis vaccine. When these components were administered alone, PT enhanced initial weight gains of the mice, LPS produced an initial weight loss and FHA had no detectable effect on the weights of the mice. However, testing the components in combinations revealed that the effect of PT and LPS together was not simply the sum of their individual effects. This combination generally produced lower weights than LPS alone, particularly in the later stages of the test.

Animals↗

An assay of Bordetella pertussis adhesion to tissue-culture cells.

The ability of Bordetella pertussis to bind to cell surfaces was determined with a simple, accurate, reproducible assay measuring the adhesion of radiolabelled bacteria to monolayers of HeLa cells. The rate of adhesion was approximately linear with time for at least 1 h. Viable and radioactivity counts of bound bacteria correlated well. Bacteria grown in the avirulent C-mode were markedly less adhesive than virulent X-mode cells. Reductions in the level of attachment after treatment of bacteria with preparations of specific immunoglobulin suggest that adhesion of B. pertussis depends upon specific mechanisms involving filamentous haemagglutinin and the agglutinogens.

Adhesiveness↗

Serum antibody responses to the outer membrane proteins of Bordetella pertussis.

The serum antibody responses to the outer membrane proteins, purified filamentous hemagglutinin, and leukocytosis-promoting factor of Bordetella pertussis were examined in mice and children immunized with pertussis whole-cell vaccine. It was found that, although there were many similarities in the responses of mice and children, there were important differences. Sera from vaccinated mice reacted strongly with purified filamentous hemagglutinin and gave weak or undetectable responses to the components of purified leukocytosis-promoting factor. The converse was found with sera from vaccinated children. Antibodies to leukocytosis-promoting factor may thus be of importance in protecting children against pertussis, although they appear to play no role in the active mouse protection test for vaccine efficacy. These results cast doubt on the value of the mouse as an animal model for the potency testing of extracted acellular pertussis vaccines.

Animals↗

Isolation and properties of an inducible and a constitutive beta-lactamase from Pseudomonas aeruginosa.

The inducible beta-lactamase from Pseudomonas aeruginosa NCTC 8203 and the constitutive beta-lactamase from strain 1822 S/H have been isolated and compared. These two enzymes are apparently periplasmic since they are released by freezing and thawing. They resemble each other closely in their molecular weights, amino acid composition, isoelectric points and electrophoretic mobility as well as in their catalytic properties, and they may be identical. Neither enzyme contains a free thiol group.

Amino Acids↗

Isolation and properties of fungi that lyse blue-green algae.

Of 70 pure microbial cultures isolated from aquatic habitats, soil, and air according to the ability to lyse live blue-green algae, 62 were fungi representing the genera Acremonium, Emericellopsis, and Verticillium. Algal-lysing fungi were isolated from all habitat types sampled. The remaining isolates comprised four bacteria and four streptomycetes. All isolates lysed Anabaena flos-aquae and, in most cases, several other filamentous and unicellular blue-green algae. The fungi generally showed greater activity than most other isolates towards a wider range of susceptible algae, including green algae in some cases. Acremonium and Emericellopsis isolates, but not Verticillium, also inhibited the growth of blue-green algae and gram-positive bacteria, but did not lyse the latter. Lysis of blue green algae by Acremonium and Emericellopsis spp. was associated with the formation of diffusible heat-stable extracellular factors which, evidence suggests, could be cephalosporin antibiotic(s). Blue-green algae were also lysed by pure cephalosporin C. The frequent isolation of lytic fungi from algal habitats suggests a possible natural algal-destroying role for such fungi, which might be exploitable for algal bloom control.

Air Microbiology↗