Objectives: Pertussis vaccines containing a whole-cell pertussis component have effectively controlled pertussis disease in the US. In recent years, there has been considerable effort aimed at development of less reactogenic acellular pertussis vaccines. Vaccine development has been hindered by the lack of a laboratory correlate of clinical protection and standardized assays for measurement of immune responses. To address this need, the Laboratory has undertaken the following projects: a) To develop new assays with the goal of defining a serologic correlate of clinical protection. b) To work toward the international standardization of ELISA's used to evaluate the antigen and isotype specific responses to B. pertussis. c) To employ these assays to evaluate the serologic response in individuals either vaccinated with pertussis vaccine or infected with B. pertussis and in animal models of infection. FY96 activities: 1. Completed evaluation of an international collaborative study to evaluate immunoassays used in acellular pertussis vaccine efficacy and immunogenicity studies. A panel of serum samples was sent to participating laboratories in 12 countries and data was received from 33 laboratories. A technical report has been sent to collaborators and a manuscript has been accepted for publication. 2. Worked with university, foreign and manufacturer laboratories to transfer the standardized assays so that these laboratories could use the assays to evaluate the serologic response in clinical trials. 3. Continued analysis of immunoassay results on a sub-group of individuals from an NIAID study who received licensed whole cell pertussis vaccine as a primary and one of the 12 different acellular vaccines as a fourth dose. 4. 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 T-neutralization activity as measured in a tissue culture assay and PT-binding activity as measured by ELISA. 5. Completed a pilot study in which quality of human immune responses was evaluated by determining antibody avidity following B. pertussis infection or vaccination with acellular pertussis vaccines.
