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. Using this model, we have previously shown that pertactin and the B oligomer of pertussis toxin, both components of acellular pertussis vaccines recently tested in clinical efficacy trials, are protective antigens. Our current work focuses on an antigen that is present in acellular pertussis vaccines, a high molecular weight adhesin known as filamentous hemagglutinin or FHA. FHA has been shown to be an important protective antigen in clinical trials, but serum antibody titers to FHA do not correlate with vaccine mediated protection against disease. An 18 kDa polypeptide corresponding to residues 1141 to 1279 of FHA, expressed in E. coli by Prasad et al (Infect. Immun. 60: 2780-2785), is known as Fragment A and is proposed to be a carbohydrate recognition domain which mediates bacterial adherence. Fragment A, purified from E. coli lysates over CM sepharose, used to immunize mice subcutaneously, induces high titers of specific antibody which reacts with both FHA and Fragment A in ELISA assays. Experiments are now in progress to determine if parenteral or mucosal immunization with Fragment A will protect against B. pertussis respiratory infection.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BJ003004-06
Application #
5200686
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost