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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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Trafficking of neutrophils across airway epithelium is dependent upon both thioredoxin- and pertussis toxin-sensitive signaling mechanisms.
L. A. Miller, J. Usachenko, R. J. McDonald, and D. M. Hyde (2000)
J. Leukoc. Biol. 68, 201-208
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Infect. Immun. 68, 1276-1281
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Intracellular Delivery of a Cytolytic T-Lymphocyte Epitope Peptide by Pertussis Toxin to Major Histocompatibility Complex Class I without Involvement of the Cytosolic Class I Antigen Processing Pathway.
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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.
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A Controlled Trial of Two Acellular Vaccines and One Whole-Cell Vaccine against Pertussis.
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WHOOPING-COUGH VACCINE UPDATE.
(1989)
Journal Watch (General) 1989, 6
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Science. ISSN 0036-8075 (print), 1095-9203 (online)