Two major problems pertaining to current efforts to develop clinical pneumococcal polysaccharide-protein vaccines are: 1) variation in the immunogenicity of conjugate vaccines even when the carrier remains the same and 2) the unpredictable effects of carrier priming including suppression of the anti-polysaccharide antibody response in some cases. The proposed studies are designed to elucidate the immunologic mechanisms responsible for variation in polysaccharide-protein conjugate immunogenicity when different polysaccharides are coupled to the same carrier and to determine conditions that maximize the ability of carrier priming to boost the protective antibody response to subsequent polysaccharide-carrier immunizations.
In Specific Aim 1, variations in immunogenicity of three pneumococcal polysaccharide-protein conjugates will be documented by assays of serum antibody and T cell responsiveness in mice.
In Specific Aim 2, the influence of the polysaccharide in altering processing of the carrier protein by class II MHC molecules will be determined. A second aspect of Specific Aim 2 involves the role of Ps-specific precursor frequency in the induction of the immune response to the polysaccharide-protein conjugate.
In Specific Aim 3, the roles of different types of antigen presenting cells (activated B cells, macrophages, and dendritic cells) and the patterns of T cell-derived cytokines elicited by the different antigen-presenting cells will be analyzed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041657-05
Application #
6373677
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Klein, David L
Project Start
1997-09-15
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2003-08-31
Support Year
5
Fiscal Year
2001
Total Cost
$241,492
Indirect Cost
Name
Case Western Reserve University
Department
Pathology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106