Objectives: Although pertussis vaccines containing a whole-cell pertussis component effectively controlled pertussis disease in the US, safety concerns led to an international research and development effort that resulted in the US licensure in 1996-1998 of four DTP products with an acellular pertussis component. Progress in the development and licensing of less reactogenic acellular pertussis vaccines, as well as combination vaccines containing an acellular pertussis component, was hindered by the lack of a laboratory correlate of clinical protection and of standardized assays for measurement of immune responses. To address this need, the Laboratory has continued a long term research project with the following aims: a) To work toward the international standardization of immunoassays used to evaluate the antigen and isotype specific responses to Bordetella pertussis. b) To employ these assays to evaluate the serologic response in individuals immunized with pertussis vaccine. c) To develop new assays and animal models with the goal of defining a laboratory correlate of clinical protection. FY99 activities: 1. For an ongoing NIAID study, completed analysis of a sub-group of individuals (n = 350) who received one of 6 different acellular vaccines as a fifth dose. Although, the laboratory did not perform the primary serologic assays, our laboratory performed approximately 600 assays on subsets of samples for quality control purposes and took a lead role in the analyses and publication of the safety and immunogenicity data. 2. Participated in the analyses of immunological data from those children in the NIAID multicenter trials who experienced an extensive swelling reaction following a fourth or fifth consecutive dose of DTaP vaccine. 3. Continued evaluation of a mouse leukocytosis model which is able to detect pertussis toxin (PT)-neutralizing antibodies in human serum, and to correlate these results with PT-neutralization activity as measured in a tissue culture assay and PT-binding activity as measured by ELISA. 4. Paricipated in an international collaborative study of the proposed First International Standard Mouse Antipertussis Serum. CBER also assisted in the study design and provided the US Standard Pertussis Antiserum (mouse) that was the primary calibrator. 5. In a collaboration with National Institute for Biological Standardization and Control (NIBSC, United Kingdom), performed approximately 125 assays comparing antibodies to Bordetella pertussis fimbriae in a proposed WHO mouse reference anti-pertussis serum and in the US Reference Pertussis Antiserum (mouse). 6. Continued evaluation of the data from a previously published international collaborative study that evaluated immunoassays used in acellular pertussis vaccine efficacy and immunogenicity studies. The goal is to determine which statistical models most accurately describe and define ELISA assay variability.
