This project involves performing studies directed towards the development of vaccines using recombinant DNA technology to synthesize immunogenic peptides from microbial agents. The objective is to identify specific natural or genetically modified proteins which when used as immunogens will protect against challenge by Bordetella pertussis, the causative agent of whooping cough. These antigens will then be considered for use in a new generation consisting of five subunits, which is a major protective immunogen in whooping cough vaccines. Our initial effort involves evaluating individual subunits of pertussis toxin produced synthetically using recombinant DNA technology. Our earliest results suggested that the standard mouse lethal intracerebral challenge (ic) model was incapable of reliably identifying protective pertussis components and are variably reliable in demonstrating protection with a commercial available whole cell vaccine. By modifying the ic challenge to include a small dose of active pertussis toxin, which is incapable of stimulating immunoprotection following immunization with both purified components and recombinant component subunits. However, mice immunized with the recombinant subunits with added subimmunogenic doses of pertussis toxin were unable to mount a response that protected them from the pathophysiologic effects of the toxin. The results suggest that anti-subunit antibodies may play roles in preventing disease other than those involving the neutralization of pertussis toxin activity.
