PERTUSSIS TOXIN--AN APPROACH TO A NEW PERTUSSIS VACCINE

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The incidence of pertussis has been controlled by use of our current whole cell pertussis vaccines. Recent advances in identification of pertussis toxin (PT) as a major protective antigen against pertussis affords and opportunity to produce a new vaccine with improved safety and efficacy. Project Z01 HD 01302 is directed at characterizing the biochemical action of PT; the current project concentrates on development of mnethods for production of PT, as well as methods for neutralization of toxic action and assessing the immune response to toxins thus neutralized. Growth conditions and purification methods scale production of PT under conditions that are suitable for human usage. B. pertussis cultivated in a 100 1 fermentator, yields more than 200 mg of purified PT. This level of PT production makes practical the preparations of experimental vaccines in sufficient quantities to permit clinical trail. Assay methods for monitoring the toxicity and neutralization of toxicity of experimental vaccine preparation have been established. In addition, methods have been established to monitor the retained antigenicity of toxoided PT preparations, and to monitor immue response to PT-toxoids in mice, monkeys, and humans, and also to measure vaccine efficacy in mice and tissue culture. Experimental pertussis vaccines have been developed which show only minimal levels of residual toxic activities, while antigenic activity is only partially reduced. Experimental vaccines prepared by absorption of pertussis toxoid onto aluminum hydroxide are highly antigenic and elicit a PT specific immune response. Immunization with this pertussis toxoid protects mice against both bacterial and toxin challenge, elicits serum antibodies which neutralizes PT in the CHO cell assay. These data predict that this pertussis toxoid will be effective in the prevention of pertussis.