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Science 27 October 1989:
Vol. 246. no. 4929, pp. 497 - 500
DOI: 10.1126/science.2683073
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Articles

Science, Vol 246, Issue 4929, 497-500
Copyright © 1989 by American Association for the Advancement of Science

articles

Mutants of pertussis toxin suitable for vaccine development

M Pizza, A Covacci, A Bartoloni, M Perugini, L Nencioni, MT De Magistris, L Villa, D Nucci, R Manetti, M Bugnoli, and al. et

Sclavo Research Center, Siena, Italy.

Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles of the pertussis toxin genes, constructed by replacing either one or two key amino acids within the enzymatically active S1 subunit, were introduced into the chromosome of strains of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. These strains produce mutant pertussis toxin molecules that are nontoxic and immunogenic and that protect mice from the intracerebral challenge with virulent Bordetella pertussis. Such molecules are ideal for the development of new and safer vaccines against whooping cough.


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Parenteral immunization of mice with a genetically inactivated pertussis toxin DNA vaccine induces cell-mediated immunity and protection.
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Evading the Proteasome: Absence of Lysine Residues Contributes to Pertussis Toxin Activity by Evasion of Proteasome Degradation.
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Pertussis Toxin Targets Airway Macrophages To Promote Bordetella pertussis Infection of the Respiratory Tract.
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Counterselectable Markers: Untapped Tools for Bacterial Genetics and Pathogenesis.
J.-M. Reyrat, V. Pelicic, B. Gicquel, and R. Rappuoli (1998)
Infect. Immun. 66, 4011-4017
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A Murine Model in Which Protection Correlates with Pertussis Vaccine Efficacy in Children Reveals Complementary Roles for Humoral and Cell-Mediated Immunity in Protection against Bordetella pertussis.
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Molecular Mechanisms of Lymphocyte Homing to Peripheral Lymph Nodes.
R. A. Warnock, S. Askari, E. C. Butcher, and U. H. v. Andrian (1998)
J. Exp. Med. 187, 205-216
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Pertussis Vaccine Encephalopathy.
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Allergy and Immunology.
S. C. Bukantz and R. F. Lockey (1990)
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Peptide immunogen mimicry of a protein-specific structural epitope on human choriogonadotropin.
J. Bidart, F Troalen, P Ghillani, N Rouas, A Razafindratsita, C Bohuon, and D Bellet (1990)
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WHOOPING-COUGH VACCINE UPDATE.
(1989)
Journal Watch (General) 1989, 6
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From the Cover: The transcriptional responses of respiratory epithelial cells to Bordetella pertussis reveal host defensive and pathogen counter-defensive strategies.
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