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Pertussis toxin glutaraldehyde

Chun-Ting Yuen, Catpagavalli Asokanathan, Sarah Cook, Naomi Lin, Dorothy Xing
Pertussis toxin (PTx) is a major virulence factor produced by Bordetella pertussis and its detoxified form is one of the major protective antigens in vaccines against whooping cough. Ideally, PTx in the vaccine should be completely detoxified while still preserving immunogenicity. However, this may not always be the case. Due to multilevel reaction mechanisms of chemical detoxification that act on different molecular sites and with different production processes, it is difficult to define a molecular characteristic of a pertussis toxoid...
April 19, 2016: Vaccine
Anja Seubert, Ugo D'Oro, Maria Scarselli, Mariagrazia Pizza
Pertussis toxin (PT) is one of the major virulence factors of Bordetella pertussis and the primary component of all pertussis vaccines available to date. Because of its various noxious effects the toxin needs to be detoxified. In all currently available vaccines, detoxification is achieved by treatment with high quantity of chemical agents such as formaldehyde, glutaraldehyde or hydrogen peroxide. Although effective in detoxification, this chemical treatment alters dramatically the immunological properties of the toxin...
October 2014: Expert Review of Vaccines
Birgit Thierry-Carstensen, Tine Dalby, Michael A Stevner, John B Robbins, Rachel Schneerson, Birger Trollfors
Combination vaccines containing a monocomponent acellular pertussis (aP) vaccine, manufactured at Statens Serum Institut (SSI), Denmark, have successfully controlled Bordetella pertussis infections in Denmark since 1997. The efficacy of this aP vaccine was 71% in a double-blind, randomised and controlled clinical trial. Its safety and immunogenicity have been demonstrated in infants, children, adolescents and adults. In approximately 500,000 children it was effective against pertussis requiring hospitalisation (VE: 93% after 3 doses) and against pertussis not requiring hospitalisation (VE: 78% after 3 doses)...
October 25, 2013: Vaccine
Hokyung Oh, Byoung-Guk Kim, Kyung-Tak Nam, Seung-Hwa Hong, Dong-Ho Ahn, Gi-Sub Choi, Hyungjin Kim, Jin-Tae Hong, Byung-Yoon Ahn
Pertussis toxin (PTx) is an essential component of the acellular pertussis (aP) vaccine. However, because PTx in its native form is considered too toxic for human vaccine use, it must be inactivated into a stable, nontoxic form by treatment with chemical detoxifying agents or by genetic modification. Therefore, testing for the residual PTx in the aP vaccine is a major quality control step for vaccine manufacturers and regulatory authorities. The histamine sensitization test is currently the standard safety test method for all aP vaccines, regardless of the vaccine formula or the detoxification process, except for those with genetically modified PTx...
June 24, 2013: Vaccine
Yajun Tan, Roland A Fleck, Catpagavalli Asokanathan, Chun-Ting Yuen, Dorothy Xing, Shumin Zhang, Junzhi Wang
Pertussis toxin in its detoxified form is a major component of all current acellular pertussis vaccines. Here we report the membrane translocation and internalization activities of pertussis toxin and various pertussis toxoids using Chinese hamster ovary cells and confocal microscopy based on indirect immunofluorescence labeling. Chemically detoxified pertussis toxoids were able to translocate/internalize into cells at the concentration about 1,000 times higher than the native toxin. Pertussis toxoids detoxified with different procedures (glutaraldehyde, glutaraldehyde plus formaldehyde, hydrogen peroxide or genetic mutation) showed differences in fluorescence intensity under the same condition, indicating toxoids from different detoxification methods may have different translocation/internalization activities on cells...
February 2013: Human Vaccines & Immunotherapeutics
Nadège Moreno, Michel Chevalier, Frédéric Ronzon, Catherine Manin, Monique Dupuy, Tino Krell, Jean-Paul Rieu
An inactivated form of pertussis toxin (PTX) is the primary component of currently available acellular vaccines against Bordetella pertussis, the causative agent of whooping cough. The PTX analyzed here is purified at industrial scale and is subsequently inactivated using glutaraldehyde. The influence of this treatment on antibody recognition is of crucial importance and is analyzed in this study. Surface plasmon resonance (SPR) experiments using PTX and its inactivated form (toxoid) with 10 different monoclonal antibodies were conducted...
November 2011: Journal of Molecular Recognition: JMR
F Simondon, A Yam, J Y Gagnepain, S Wassilak, B Danve, M Cadoz
A diphtheria and tetanus toxoid two-component acellular pertussis vaccine (DTaP), consisting of 25 micrograms glutaraldehyde-detoxified pertussis toxin (PT) and 25 micrograms native filamentous hemagglutinin (FHA), was compared with diphtheria and tetanus toxoid whole-cell pertussis vaccine (DTwP) in a randomized, double-blind manner in 286 Senegalese infants inoculated at two, four, and six months of age. In infants receiving DTaP a significantly lower rate of local reactions, crying and fever was observed than in infants receiving DTwP...
December 1996: European Journal of Clinical Microbiology & Infectious Diseases
D Greco, S Salmaso, P Mastrantonio, M Giuliano, A E Tozzi, A Anemona, M L Ciofi degli Atti, A Giammanco, P Panei, W C Blackwelder, D L Klein, S G Wassilak
BACKGROUND: Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low. METHODS: We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT)...
February 8, 1996: New England Journal of Medicine
O Jeanneton, M Delvaux, A Botella, J Frexinos, L Bueno
This study was designed to evaluate the effect of platelet-activating factor (PAF) on isolated smooth muscle cells from guinea pig ileum circular layer, to characterize the PAF receptors involved in this effect and to determine the intracellular pathways triggered by PAF. Cells dispersed by enzymatic digestion were incubated for 30 sec in the presence of PAF and fixed by glutaraldehyde. When inhibitors or antagonists were tested, cells were preincubated with them for 1 min. Then PAF was added for 30 sec, and the cells were fixed...
October 1993: Journal of Pharmacology and Experimental Therapeutics
S P Mitra, R E Carraway
Using 125I-labeled neurotensin (NT), chicken liver was found to contain high affinity, G-protein-linked receptors directed specifically towards the bioactive C-terminal portion of NT. Binding was proportional to membrane and optimal at pH 7.5. The apparent Kd (approximately 91 pM) for this single class of binding sites was similar to Kds reported for the high-affinity components of NT binding to mammalian brain and intestinal membranes. However, the binding capacity (Bmax, approximately 2.3 pmol/mg) was 10-100 times higher than values reported for these mammalian tissues...
1995: Peptides
W O Dias, D S Horton, C M Takahashi, I Raw
A single-step chromatography on Matrex-Gel Blue A has been employed to obtain soluble extracts containing some of the most important antigens of Bordetella pertussis, pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (69-kDa outer membrane protein), fimbriae (FIM2 and FIM3) and adenylate cyclase (AC). Two supernatants, P19 (48.8 mg PT, 6.8 mg FHA, 17.3 mg AC, 13 mg FIM2 and 4.9 mg FIM3 per liter) and P21 (0.1 mg PT, 0.07 mg FHA, 0.46 mg FIM2 and 0.94 mg FIM3 per liter), resulting from bacteria grown in Stainer-Scholte medium, were submitted to chromatography...
November 1994: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
E H Relyveld, S Ben-Efraim
No abstract text is available yet for this article.
1983: Methods in Enzymology
A Robinson, L I Irons
The effect of low levels of added lymphocytosis-promoting factor (LPF) on the ability of several antigenic preparations isolated from Bordetella pertussis and other bacteria to protect mice against intracerebral infection with B. pertussis was examined. LPF was found to enhance the protective activities of filamentous hemagglutinin, 22S antigen, and fimbriae isolated from B. pertussis. Outer membrane protein preparations from phase I B. pertussis which had LPF removed by haptoglobin affinity columns or inactivated by glutaraldehyde, sodium dodecyl sulfate, or Formalin had reduced protective activities but were made fully protective by the readdition of LPF...
May 1983: Infection and Immunity
A Robinson, D C Hawkins
The structure and biological properties of solubilized envelope proteins of Bordetella pertussis have been examined. Several envelope proteins were found to be specific for phase I strains of B. pertussis and could be isolated by selective detergent extraction. These proteins had molecular weights of 90,000, 86,000, 81,000, 33,000, 31,000, and 30,000 and were reduced or absent in envelope preparations from Bordetella bronchiseptica, Bordetella parapertussis, or phase IV strains of B. pertussis. When the envelope preparations from phase I B...
February 1983: Infection and Immunity
J J Munoz, H Arai, R K Bergman, P L Sadowski
We studied various biological activities of crystalline pertussigen and found that in mice as little as 0.5 ng of pertussigen induced hypersensitivity to histamine, 8 to 40 ng induced leukocytosis, 2 ng increased production of insulin, 0.1 ng increased production of immunoglobulin E and immunoglobulin G1 antibodies to hen egg albumin, 9.5 ng increased susceptibility to anaphylactic shock, and 0.5 ng increased the vascular permeability of striated muscle. We also found that in Lewis rats 20 ng of pertussigen promoted the induction of hyperacute experimental allergic encephalomyelitis...
September 1981: Infection and Immunity
J J Munoz, H Arai, R L Cole
We compared the protective activities of fimbrial hemagglutinin (FHA) and pertussigen and their respective antibodies in mice infected intracerebrally with Bordetella pertussis. We found that mice were protected by a 1.7-microgram/mouse dose of pertussigen which was free of detectable FHA and was detoxified by treatment with glutaraldehyde. A pertussigen preparation made from cells grown in shake cultures that did not contain demonstrable FHA protected mice at a dose of 1.4 microgram/mouse. FHA at a dose of 10 microgram/mouse protected mice from intracerebral infection, but it also sensitized mice to histamine at a dose of 2 micrograms/mouse, which indicated that it was contaminated with pertussigen...
April 1981: Infection and Immunity
M Oda, J L Cowell, D G Burstyn, C R Manclark
Protective activities of the filamentous hemagglutinin (FHA) and the lymphocytosis-promoting factor (LPF) of Bordetella pertussis were compared by active and passive protection tests with intracerebral or respiratory challenge in mice. Mice immunized twice by intraperitoneal injection of 8 micrograms of FHA or glutaraldehyde-inactivated LPF were protected after aerosol challenge. One intraperitoneal injection of inactivated LPF also protected mice from intracerebral challenge; the dose protecting 50% of the mice was 8...
December 1984: Journal of Infectious Diseases
M Watanabe
Pertussigen prepared from Bordetella pertussis strains of various agglutinogen types was found to have similar biological activities in mice, and to give precipitin lines of identity in agar diffusion tests. The doses required to induce histamine hypersensitivity ranged from 0.9 to 9.5 ng, and to induce leukocytosis from 124 to 190 ng. When pertussigen was detoxified by treatment with glutaraldehyde, it protected mice from intracerebral challenge with B. pertussis at doses of from 12.7 to 24.4 micrograms. The results showed that all smooth strains of B...
1984: Microbiology and Immunology
M J Quentin-Millet, F Arminjon, B Danve, M Cadoz, J Armand
An animal model has been developed to assess the safety of acellular pertussis vaccines in terms of reversion to toxicity. Adsorbed pertussis toxoid preparations, alone or combined in a DTP formulation, were administered to nude mice intraperitoneally. In parallel, groups of positive and negative control mice received pertussis toxin and buffer, respectively. The circulating white blood cells of the animals were monitored for 28 days. Mice immunized with glutaraldehyde toxoid preparations did not develop a lymphocytosis during the observation period, whereas mice immunized with an experimental formalin pertussis toxoid vaccine exhibited a high lymphocytosis six days after vaccine administration, demonstrating, in this model, a reversion of the toxoid...
April 1988: Journal of Biological Standardization
R K Gupta, S B Sharma, S Ahuja, S N Saxena
The effects of different inactivating agents on the biological activity of the histamine sensitization factor of Bordetella pertussis toxin were examined. The agents were used for inactivation in the preparation of whole cell pertussis suspension. The histamine sensitizing activity was reduced to 36.9-13.3% by treatment with glutaraldehyde, to about 50% by treatment with formaldehyde and by the acetone-II treatment, relative to the reduction by heat treatment. Treatment with thimerosal and the acetone-I treatment did not reduce the histamine sensitizing activity as the 50% histamine sensitizing doses of the heat inactivated pertussis preparation, the thimerosal inactivated pertussis preparation and the acetone-I treated pertussis preparation were very similar...
April 1987: Journal of Biological Standardization
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