Local, systemic and neurological complications have been observed following pertussis (whooping cough) vaccination in children. These often occur soon after primary or secondary immunization. The neurological syndrome ranges from minor irritability to convulsions, coma, and on rare occasions death. Children who recover show varying degrees of permanent neurological sequelae. The pathogenesis of this encephalopathy is unknown, and the lack of an animal model has retarded our understanding of this disease. We have described an animal model for pertussis immunization encephalopathy. A clinical syndrome with pathological features closely resembling post-immunization encephalopathy can be reproduced in the mouse after immunization with heat-killed Bordetella pertussis vaccine and exposure to a foreign antigen, if the inoculated animal has a susceptible H-2 genotype. We will analyze the mechanisms whereby B. pertussis immunization produces encephalopathy in four major areas. Genetic mapping studies will localize the locus of susceptibility to encephalopathy within H-2. Immunologic experiments will a) study the role of antibody isotype using switch variants of monoclonal antibodies, b) ascertain whether transposon induced B. pertussis mutants are adequate vaccines, and c) analyze the characteristics of pertussis triggered lymphocytosis. Therapy of B. pertussis encephalopathy will be tried with anti-I-A and anti-L3T4 antibody. Physiologic studies on B. pertussis dependent T cell homing to the central nervous systmem will be carried out. These experiments may help to characterize the rare encephalopathic reactions to B. pertussis and may lead to the development of a safer B. pertussis vaccine.
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