Animal models are used for the evaluation of the safety and immunogenicity of acellular pertussis vaccine candidates before use in clinical trials and administration to humans. The aerosol challenge model provides a reproducible system for the study of virulence factors and immunity involved in respiratory infection and subsequent disease. Recent clinical trials show that acellular pertussis antigens are protective against disease; however serum antibody titers to pertussis antigens, do not correlate with vaccine mediated protection. One reason for this may that pertussis specific antibodies in respiratory secretions rather than serum antibody may better reflect protective immunity to pertussis infection. We are characterizing the roles of IgG and IgA in mucosal secretions in protecting against B. pertussis infection. We have generated 2 IgA monoclonal antibodies to filamentous hemagglutinin (FHA), one component of acellular pertussis vaccines, and will characterize these as well as IgG anti-FHA antibodies for affinity, epitope specificity, in vitro effector function, as well as for the ability to protect neonatal mice from pertussis infection. We are also investigating the ability of pertussis specific antibodies in mother's milk to protect against infection. Future experiments will examine the ability of engineered monoclonal antibodies, in which gamma heavy chain of a protective monoclonal antibody is replaced with an alpha heavy chain gene to protect against pertussis infection.
