Role of Pertussigen (Pertussis Toxin) on the Mouse Protective Activity of Vaccines Made from <i>Bordetella</i> Species

Muñoz, J.; Peacock, Marius G.

doi:10.1111/j.1348-0421.1989.tb01982.x

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…Among the striking number of known virulence factors exhibited by virulent B. pertussis organisms, the exotoxin PT is regarded as one of the major factors involved in the development of the pathology of the human respiratory disease whooping cough, acting not only as an exotoxin but also as an agglutinin (21,22,39). Contaminating active toxin has been held responsible for the rare, but sometimes severe, complications attributed to pertussis vaccination with the current whole-cell pertussis vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Virulent Bordetella pertussis organisms exhibit a remarkable array of virulence factors which promote the development of the human respiratory disease whooping cough. Besides cell surface-associated factors such as pili and the filamentous hemagglutinin (32), B. pertussis also produces a number of toxins such as pertussis toxin (PT), adenylate cyclase toxin, tracheal cytotoxin, and dermonecrotic toxin (17,21,22,45,46). The expression of the majority of the known virulence factors has been found to be coordinately regulated (9,18,34).…”

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confidence: 99%

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Identification of linear B-cell determinants of pertussis toxin associated with the receptor recognition site of the S3 subunit

et al. 1991

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Receptor recognition of pertussis toxin is mediated by the B oligomer consisting of subunits S2, S3, 2xS4, and S5. One possible way to interfere with toxin action would be the inhibition of recognition and binding of the cellular receptor(s) by preformed toxin-directed antipeptide antibodies. A prerequisite for this approach is the localization of linear antigenic determinants followed by the identification of inhibitory epitopes. Anti-S2 peptide antibodies have been shown to inhibit binding of the holotoxin to in vitro model receptor systems. For the elucidation of linear antigenic and immunogenic determinants harbored in the S3 subunit, synthetic peptides corresponding to selected linear amino acid sequences of S3 have been prepared and used to raise peptide-specific antibodies in rabbits. All peptides elicited a strong homologous response. Four synthetic peptides reacting with anti-pertussis toxin antibodies (R36-51, R87-95, R134-150, and R147-160) have been identified. Seven synthetic peptides (Rl-12, R12-23, R14-29m, R36-51, R95-107, R134-150, and R164-178) induced antibodies recognizing pertussis toxin. Thus, these segments correspond to linear antigenic determinants. Analogous to the S2 subunit, the N terminus of S3 proved to be immunorecessive in the native toxin. The highly homologous S2 subunit was only bound strongly in Western blotting (immunoblotting) by antiserum directed at peptide R164-178, which is identical in the S2 and S3 subunits. A weak recognition of S2 in Western blotting was observed with anti-R95-107 antiserum. The ability of affinity-purified anti-S3 peptide antibodies to interfere with pertussis toxin binding was investigated by hemagglutination of goose erythrocytes as a model receptor system for S3-mediated receptor recognition. Antipeptide antibodies directed at Rl-12, R12-23, R14-29m, and R36-51 inhibited hemagglutination of goose erythrocytes. This indicates that the corresponding antigenic regions in the S3 subunit are associated with the formation of the receptor binding domain. Inhibition of B-oligomer-mediated pertussis toxin binding to cellular receptors by preformed antipeptide antibodies of sufficient affinity should not only block the detrimental effects of the Si subunits, but also interfere with the mitogenic effects attributed to the B oligomer.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Identification of linear B-cell determinants of pertussis toxin associated with the receptor recognition site of the S3 subunit

et al. 1991

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“…Whole-cell pertussis vaccine and purified PT are known to possess adjuvant activities and have been used by immunologists and pharmacologists to enhance the immunological responses to many antigens (15,16). Based on this, it has been often speculated that the potency of the whole-cell pertussis vaccine is also due to the presence of active PT (1,14).…”

Section: Discussionmentioning

confidence: 99%

“…A vaccine devoid of active PT would be preferable and would avoid the inoculation of children with a toxin which is known to cause many harmful effects. However, reports in the literature suggest that active PT is necessary for the potency of the whole-cell vaccine (1,14). To overcome the problems associated with pertussis vaccination, acellular vaccines devoid of active PT are being developed and tested in clinical trials.…”

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confidence: 99%

Cellular pertussis vaccine containing a Bordetella pertussis strain that produces a nontoxic pertussis toxin molecule

Marsili¹,

Pizza²,

Giovannoni³

et al. 1992

Infect Immun

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Bordetella pertussis 165-9K/129G, which produces a nontoxic form of pertussis toxin (PT), was used to prepare a whole-cell diphtheria-tetanus-pertussis (DTP) vaccine. The in vivo potency and the serological response induced by this vaccine were comparable to those of the conventional DTP vaccine which contains active PT. The toxic activities induced by PT such as leukocytosis, histamine sensitivity, and potentiation of anaphylactic reactions, which are present in the conventional DTP vaccine, were absent in the new vaccine. These results suggest that the introduction of a whole-cell vaccine containing B. pertussis 165-9K/129G would induce the same immunity as the conventional vaccine and would avoid the administration of a harmful toxin to children.

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“…The expression of the majority of the known virulence factors has been shown to be coordinately regulated [3][4][5]. In mice, most of the symptoms of whooping cough can be induced by the action of PT alone [6][7][8][9] Furthermore, PT also seems to be largely responsible for the systemic pathology in the human host [10,11]. Thus, PT is regarded as the major virulence factor of B. pertussis [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Characterization of monoclonal antibodies directed against domains of pertussis toxin involved in receptor recognition

Schmidt

Seitz

Burk

1991

FEMS Microbiology Letters

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Summary The exotoxin pertussis toxin (PT) produced by virulent Bordetella pertussis bacteria is regarded as the main virulence factor of the organism and held responsible for most of its pathological effects. Identification of functional sites on PT would greatly facilitate site‐specific detoxification and thus also the development of a new vaccine. For the investigation of structure‐function aspects of PT we have prepared and characterized eleven monoclonal antibodies (mAbs) (UB‐A1, UB‐A2, UB‐A10, UB‐B7, UB‐B12, UB‐D4, UB‐D7, UB‐D10, UB‐F7, UB‐G1, and UB‐G12) directed at the native toxin. Only UB‐B12 and UB‐D10 recognized PT in Western blotting indicating that most of the mAbs were directed against conformational epitopes. The mAbs were assayed for their ability to interfere with the binding of PT in model receptor systems like a solid phase binding assay using fetuin as receptor moiety, hemagglutination of chymotrypsin‐sensitized goose erythrocytes, and the PT‐mediated induction of the clustered growth pattern (CGP) of Chinese hamster ovary (CHO) cells. Five of the eleven mAbs (UB‐A1, UB‐A2, UB‐B7, UB‐B12, and UB‐D7) interfered with the binding of PT to fetuin on solid phase and with PT‐mediated hemagglutination. UB‐A2, UB‐B7, and UB‐B12 also inhibited the induction of the clustered growth pattern of CHO‐cells. This indicates that the determinants recognized by these mAbs are associated with the formation of the carbohydrate recognition sites of PT. Thus, the monoclonal antibodies described in this study will be valuable tools in the further analysis of the structure‐function relationship of pertussis toxin with respect to receptor recognition and binding.

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Role of Pertussigen (Pertussis Toxin) on the Mouse Protective Activity of Vaccines Made from Bordetella Species

Cited by 18 publications

References 33 publications

Identification of linear B-cell determinants of pertussis toxin associated with the receptor recognition site of the S3 subunit

Identification of linear B-cell determinants of pertussis toxin associated with the receptor recognition site of the S3 subunit

Cellular pertussis vaccine containing a Bordetella pertussis strain that produces a nontoxic pertussis toxin molecule

Characterization of monoclonal antibodies directed against domains of pertussis toxin involved in receptor recognition

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