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Science 29 April 1988:
Vol. 240. no. 4852, pp. 656 - 659
DOI: 10.1126/science.2896387
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Articles

Science, Vol 240, Issue 4852, 656-659
Copyright © 1988 by American Association for the Advancement of Science

articles

ADP-ribosyltransferase activity of pertussis toxin and immunomodulation by Bordetella pertussis

WJ Black, JJ Munoz, MG Peacock, PA Schad, JL Cowell, JJ Burchall, M Lim, A Kent, L Steinman, and S Falkow

Department of Medical Microbiology, Stanford University, CA 94305.

Pertussis toxin is produced by the causative agent of whooping cough, Bordetella pertussis, and is an adenosine diphosphate (ADP)-ribosyltransferase capable of covalently modifying and thereby inactivating many eukaryotic G proteins involved in cellular metabolism. The toxin is a principal determinant of virulence in whooping cough and is a primary candidate for an acellular pertussis vaccine, yet it is unclear whether the ADP-ribosyltransferase activity is required for both pathogenic and immunoprotective activities. A B. pertussis strain that produced an assembled pertussis holotoxin with only 1 percent of the ADP-ribosyltransferase activity of the native toxin was constructed and was found to be deficient in pathogenic activities associated with B. pertussis including induction of leukocytosis, potentiation of anaphylaxis, and stimulation of histamine sensitivity. Moreover, this mutant strain failed to function as an adjuvant and was less effective in protecting mice from intracerebral challenge infection. These data suggest that the ADP-ribosyltransferase activity is necessary for both pathogenicity and optimum immunoprotection. These findings bear directly on the design of a nontoxic pertussis vaccine.


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Mutants of pertussis toxin suitable for vaccine development.
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CAN WE MAKE A NONTOXIC PERTUSSIS VACCINE?.
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