The immunology of bordetella pertussis infection.

Despite the wealth of information on the pathogenesis, virulence and antigenicity of Bordetalla pertussis and the successful development of e#icacious acellular pertussis vaccines, the mechanism of vaccine induced protection against Bordetalla pertussis in man is still poorly understood. Using murine models, we and others have previously reported evidence of the involvement of T cells in protective immunity. Based on the observation that respiratory infection with Bordetalla pertussis induces potent and persistent immunity, we have studies the induction of T cell subsets induced by natural infection or by immunization with whole cell and acellular vaccines in children. Furthermore we have employed the murine respiratory challenge model in experiments that permitted manipulation of the immune system in an attempt to provide more direct evidence for the role of distinct arms of the immune response in protection against Bordetalla pertussis. Through collaboration with Jann Storsaeter, Lennart Nillson and Lief Gothefors in Sweden, Knut Øymar in Norway, Elizabeth Miller in London and Fiona Shackley in Oxford, we have gained access to valuable clinical samples for the assessment of cellular immune responses to Bordetalla pertussis in children. Initial investigations of cytokine production by peripheral blood T cells from children recovering from whooping cough suggested that immunity generated by natural infection is mediated by Th1 cells. Furthermore analysis of blood samples from children within 3 months or 4 years of immunization with whole cell pertussis vaccine revealed a similar cytokine profile, moderate to high levels of IFN, but undetectable IL-5. In contrast, analysis of cellular responses form children immunized with acellular vaccines demonstrated that primed T cells secreted high levels of IFNand IL-5 following specific antigen stimulation in vitro. All of the high e#icacy acellular