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 an opportunity to produce a new vaccine with improved safety and efficacy. The current project concentrates on development of methods for production of PT, as well as methods for neutralization of toxic action and assessing the immune response to the resultant pertussis toxoid vaccine. Growth conditions and purification methods have been developed to produce PT in the quantities necessary for clinical study. 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 immune response to PT-toxoids in mice, monkeys, and humans, and also to measure vaccine efficacy in mice and tissue culture. Methods have developed to inactivate pertussis toxin and prepare pertussis toxoids. Pertussis toxoids, prepared in our laboratory, 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 and elicits serum antibodies, which neutralizes PT in the CHO cell assay. Immunization of juvenile Rhesus monkeys with the vaccine leads to a similar increase in PT neutralizing antibodies. On the basis of the safety and immunogenicity in animals, a protocol for clinical investigation of the vaccine has been drafted and approved by the FDS and NIH. Clinical evaluation of the new pertussis toxoid vaccine in humans is now beginning.
