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Pertussis toxin is an exotoxin produced by Bordetella pertussis, the bacterium that causes whooping cough. It has been estimated that whooping cough still causes about 340,000 deaths of young children in the world each year,1 although in developed countries the disease has largely been controlled by vaccination. Currently used whooping cough vaccines consist of chemically-killed whole B. pertussis cells. However, media concern about the safety of these whole-cell vaccines, while not supported by the medical profession,2–4 has prompted efforts to develop a new generation of acellular whooping cough vaccines containing pure forms of protective antigens.5 Pertussis toxin (PT) induces strong protective immunity to whooping cough6,7 and has therefore been a key component of most acellular vaccines. Since residual activity of PT may have been responsible for occasional adverse reactions associated with whole-cell vaccines,8 it is best to eliminate all biological activities of the toxin before it is used in component vaccines. Chemical treatment with aldehydes may impair immunogenicity, so site-directed mutagenesis is the preferred method of inactivating the toxin. This approach requires a detailed knowledge of functional determinants. |
