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M J Corbel

Publications and source records attributed to M J Corbel.

At least 55 records · Page 3Linked to original sources
PubMed1996

Physicochemical and immunological studies on the stability of free and microsphere-encapsulated tetanus toxoid in vitro.

The stability of tetanus toxoid released from experimental, slow-release microsphere vaccines was compared with that of free toxoid under different conditions over a 3 month period. The amount of antigenicity remaining, as measured by ELISA, correlated well with loss of toxoid structure, as determined by circular dichroism and fluorescence spectroscopy. At 37 degrees C and low pH, pH 2.5 for free toxoid, or under the acidic conditions generated by the hydrolysis of fast-release microspheres, a gradual unfolding of the polypeptide chain was observed within the first few weeks with more rapid denaturation beyond 30 days.

Drug Stability↗
PubMed1996

Reasons for instability of bacterial vaccines.

Stability problems in relation to bacterial vaccines vary widely between different types of product. Killed whole cell bacterial vaccines including pertussis, cholera and typhoid vaccines generally show a high degree of stability of potency. Reversion to toxicity may occur in incompletely inactivated pertussis vaccines. Live attenuated vaccines such as BCG and Ty21a typhoid vaccines lose potency through loss of viability when exposed to adverse conditions. Both vaccines are susceptible to ultra violet radiation but Ty21a also has low thermal stability. Its fragility is probably a consequence of multiple mutations affecting structural and metabolic factors. Diphtheria and tetanus toxoids generally show high stability of potency. Reversion to toxicity may occur if the toxoiding process is inadequate. Decline in potency may result from exposure to adverse conditions, such as freezing, that affect the interaction with the adjuvant. Similar problems may be encountered with purified subunit vaccines such as acellular pertussis preparations. Some components, in particular pertussis toxin and filamentous haemagglutinin, show inherent low stability and degrade on storage at refrigerator temperatures unless stabilized by a protein cross-linking agent. Bacterial proteases carried over from the cell cultures may also be responsible for degradation of purified components. Purified bacterial polysaccharides usually show high stability if freeze-dried under appropriate conditions. Catalytic degradation may occur however, if the stabilizers are of inadequate purity. Polysaccharide-protein conjugates such as Haemophilus influenzae b (Hib) polyribosylribityl phosphate-protein conjugates show high thermal stability if freeze dried. In the liquid state, such conjugates tend to degrade by hydrolysis of the polysaccharide chains. Combined vaccines may present special stability problems because of the interaction of the various components in the liquid state. It can be difficult to freeze-dry some components of such vaccines, particularly aluminium hydroxide-adsorbed diphtheria-tetanus-pertussis (DTP) components. Slow release vaccines based on polyglycolide-factolide microspheres may show suboptimal stability of encapsulated antigen under both in vitro conditions as a result of gradual acidification through polymer hydrolysis. Vaccines based on the use of live recombinant strains to express heterologous protective antigens may present special stability problems. Apart from the carrier strains, heterologous genes carried on plasmids may be subject to spontaneous deletion under adverse conditions. These issues have received relatively little attention hitherto but are likely to achieve greater prominence as development of such preparations proceeds.

Amino Acid Sequence↗
PubMed1994

Combination of DTP and Haemophilus influenzae type b conjugate vaccines can affect laboratory evaluation of potency and immunogenicity.

A commonly used Diphtheria-Tetanus-Pertussis (whole-cell) vaccine was combined with each of three different Haemophilus influenzae type b (Hib) capsular polysaccharide vaccines. Each Hib vaccine incorporated one of three different protein conjugates: tetanus toxoid, diphtheria CRM197 toxoid or group B Neisseria meningitidis outer membrane vesicles. The effects of these combinations on the subsequent laboratory control testing were examined. The addition of the Hib vaccines had no significant effect on the reactogenicity or the potency of the whole-cell pertussis component. The potency of, and antibody responses to, the diphtheria component were also unaffected in all three combinations. However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid had dramatic effects on tetanus potency and immunogenicity when assayed in mice. This combination resulted in a five-fold potentiation of the tetanus potency and a similarly large increase in the antibody responses to tetanus toxin and toxoid. The level of the antibody response to the Hib polysaccharide in this vaccine was also elevated, more than 20-fold, as a result of the combination. Such phenomena were not evident with combinations involving the other two Hib vaccines. These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide-tetanus protein conjugate vaccine.

Animals↗
PubMed1994

Control testing of combined vaccines: a consideration of potential problems and approaches.

Vaccines comprising combinations of diphtheria, tetanus and pertussis (DTP) components with Haemophilus influenzae b polysaccharide--protein conjugates (DTP-Hib) are now available. Combinations of DTP-Hib with additional components such as inactivated poliomyelitis vaccine, hepatitis B vaccine, meningococcal and pneumococcal polysaccharide-protein conjugates are under development. Other combinations, such as Hib vaccine with meningococcal A, B and C components and possibly pneumococcal conjugates, or non-capsulated Haemophilus components combined with pneumococcal conjugates, developed against bacterial meningitis and otitis media respectively, are of potential interest. Combination vaccines against enteric infections and including potentially cholera, typhoid, ETEC, Shigella, rotavirus and possibly Campylobacter and Helicobacter components, may become available in the longer term. The control of these combinations is likely to be based on pharmacopoeial requirements for the individual components. However, the evaluation of combinations may not be straightforward and the interaction of the components with each other may influence reactogenicity, immunogenicity and stability and will complicate laboratory control tests. Indications of this have already arisen with some DTP-Hib combinations but are likely to increase as additional components are added. For example, the use of diphtheria and tetanus proteins as carriers for multiple polysaccharide conjugates may lead to excessive antitoxin production and epitope suppression of anti-polysaccharide responses. Other problems may result from competition for binding sites on adjuvant molecules. The requirements for new vaccine combinations need to be considered carefully and should not be made solely on assumptions based on the properties of individual components.

Bacterial Vaccines↗
PubMed1994

Interaction of Haemophilus influenzae type b conjugate vaccines with diphtheria-tetanus-pertussis vaccine in control tests.

The effects of combining three Haemophilus influenzae type b (Hib) capsular polysaccharide vaccines, conjugated to different proteins, with DTP vaccine on the subsequent control testing were examined. The addition of the Hib vaccines had little effect on the reactogenicity or the potency of the whole-cell pertussis component. The potency of, and antibody responses to, the diphtheria component were also unaffected in all three combinations. However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid resulted in a fivefold potentiation of the tetanus potency and large increases in the antibody responses to tetanus toxin and toxoid and Hib polysaccharide. These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide-tetanus protein conjugate vaccine.

Animals↗
PubMed1994

Botulinum toxin.

Explore the source record for details and available documents.

Animals↗
PubMed1993

The First International Standard for Antitetanus Immunoglobulin, Human; pharmaceutical evaluation and international collaborative study.

The First International Standard (IS) for Antitetanus Immunoglobulin, Human (coded 26/488) was established by the WHO Expert Committee on Biological Standardization in October 1992 on the basis of an extensive pharmaceutical evaluation and an international collaborative study. Fifteen laboratories from 15 countries performed the toxin neutralization assay in vivo in the study. Twelve laboratories also performed an alternative in vitro assay. The new International Standard is a purified human immunoglobulin containing antibodies which are able to neutralize tetanus toxin. This new standard replaces the Second International Standard for Tetanus antitoxin, Equine, for testing of human antitetanus immunoglobulin preparations used clinically as well as for titration of human serum samples for tetanus antitoxin. The new International Standard was assigned a potency of 120 International Units (IU) of Tetanus Antitoxin per ampoule on the basis of its calibration in terms of the International Unit defined by the Second International Standard for Tetanus Antitoxin, Equine by toxin neutralization assay in vivo. The same preparation was also established as the first European Pharmacopoeia Standard for Antitetanus Immunoglobulin, Human by the European Pharmacopoeia Commission, Biological Standardization Programme in March 1993.

Animals↗
PubMed1992

Agglutination of Bordetella species by lectins.

Phase I cells of Bordetella pertussis but not those of B. parapertussis, B. bronchiseptica or B. avium were agglutinated by Limulus polyphemus lectin. Most strains of B. pertussis but not those of the other species were also agglutinated by Helix pomatia lectin. In precipitation reactions between lectins and purified Bordetella lipopolysaccharide (LPS) preparations a similar pattern occurred. Lectin agglutination provides a rapid presumptive method for the differentiation of B. pertussis from B. parapertussis and other Bordetella species.

Agglutination Tests↗
PubMed1992

Lack of early antitoxin response to tetanus booster.

Tetanus immune globulin (TIG) continues to be recommended in persons with tetanus-prone wounds who have incomplete or unknown tetanus immunization status. The aim of this study was to determine whether, following a booster dose of tetanus toxoid in adults who had not been immunized in the previous 10 years, there was an antitoxin response to tetanus toxoid booster within 4 days. Thirty-one adults were investigated, baseline levels for tetanus antitoxin assayed using an ELISA technique, and an injection of adsorbed tetanus toxoid (0.5 ml) given. Blood samples for tetanus antitoxin levels were taken at daily intervals for the 4 days following immunization. Tetanus boosters following the primary course but before the present study did not significantly increase the levels of pre-study tetanus antitoxin and following the study booster there was no difference between the preboost levels and the levels on days 1 to 4. This finding indicates that the present recommendations for the use of TIG in tetanus-prone wounds are appropriate.

Adult↗
PubMed1992

Targeting of specific domains of diphtheria toxin by site-directed antibodies.

Antibodies highly selective for two functionally distinct regions of diphtheria toxin (DTx) were prepared using synthetic peptide conjugates as immunogens. Three peptides were selected for synthesis: sequence DTx141-157 on fragment A, which contains the putative protein elongation factor (EF-2) ADP-ribosyltransferase site; DTx224-237 on fragment B, selected on the basis of forming a predicted surface loop; and DTx513-526 on fragment B, forming a part of the region containing the putative receptor binding domain. All of the anti-peptide antibodies recognized the corresponding peptide, and also reacted with the toxin, specifically with the fragment containing the sequence against which they were raised, confirming the utility of this approach in generating fragment-specific antibodies. The anti-peptide antibody with the highest binding titre both to the peptide and to the native toxin was the one prepared against the sequence with the highest surface and loop likelihood indices of the three peptides selected. The similarity of the reactivity profiles with peptide and native and denatured toxin is consistent with the prediction that the region selected occurs in a surface loop and that the structure of the peptide is similar to the conformation of this region in the native protein. The epitopes for two of the anti-peptide antibodies were mapped. The results indicated that even though the antisera were raised to peptides containing 14 amino acids (aa) they were directed predominantly against a narrow region within the peptide, consisting of only 5-6 aa residues.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

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↗
PubMed1991

The effect of Schick testing on diphtheria antitoxin status.

Twenty-nine healthy persons were Schick tested as part of their occupational health examination. All but three of them had been previously immunised against diphtheria. One unimmunised person had a history of diphtheria. Blood samples were taken before and at varied intervals after the Schick tests in order to determine whether the Schick test antigen was immunogenic. Of the 29 persons tested, 21 were Schick-negative, three were Schick-positive. Four pseudoreactors were Schick-negative, one pseudoreactor was Schick-positive. Only four of the 29 had any significant rise in antitoxin titre after Schick testing. Three of these were Schick-negative, while one was a pseudoreactor who was negative at a later reading. We conclude that Schick testing is not reliably immunogenic and that, contrary to expectation, it cannot be assumed to elicit a useful booster response in previously immunised persons.

Diphtheria Antitoxin↗
PubMed1991

Identification of dye-sensitive strains of Brucella melitensis.

Strains of Brucella melitensis biovars 1, 2, and 3 isolated in India, Italy, Kuwait, Saudi Arabia, the Federal Republic of Germany, and Zimbabwe were inhibited by thionin (20 micrograms/ml) but not by basic fuchsin (20 micrograms/ml) or safranin O (200 micrograms/ml). In other respects the strains were typical of their species and biovars. The existence of dye-sensitive strains of B. melitensis suggests that the present system of classification requires modification.

Bacterial Typing Techniques↗
PubMed1990

Human antibody response to fragments A and B of diphtheria toxin and a synthetic peptide of amino acid residues 141-157 of fragment A.

Examination of a selection of serum samples from adults from two regions of England showed that 50% of men in the 16-24 years and over 55 years age groups had high titres of antibody to diphtheria toxin (DT). In contrast, only 11% of women aged 16 to over 55 years had high titres of antibody to DT. All human antisera with high anti-DT titres reacted with a synthetic peptide (SP) corresponding to the amino acids 141-157 of DT fragment A, with sera from men aged 35 to over 55 years showing the highest titres. High antibody titres to fragment A paralleled those to SP in both sexes. Titres of antibody to DT fragment B were highest in individuals with high titres to DT. In sera from both sexes immunoglobulin G1 was the predominant subclass reactive with all three antigens. However, both IgG1 and IgG4 and to a lesser extent IgG2 and IgG3 were present in immunoglobulin concentrates.

Adolescent↗
PubMed1988

Characterisation of a new phage lytic for both smooth and non-smooth Brucella species.

A brucella phage of the Izatnagar series, designated Iz1, was lytic for all Brucella species that are normally smooth, although the efficiency of plating varied between biovars and species. The phage was also lytic for rough strains of B melitensis and B suis and, to a lesser extent, B ovis. It displayed negligible lytic activity towards B canis and rough B abortus cultures. In its morphological and serological properties and its stability to inactivating agents, the Iz1 phage resembled other brucella phages.

Bacteriophages↗