The major focus of this renewal application is to continue studies of the major defined cell surface localized protein antigen of group B streptococci, specifically the c (formerly Ibc, (composed of trypsin-resistant (TR) and trypsin-sensitive (TS) components) and R proteins of group B streptococci (GBS). This will involve further purification of the components of the c protein, as well as the IgA binding protein that has been identified, and to assess the role of antibodies to these protein as host defense mechanisms against infection with strains possessing the protein antigenic markers. The contribution of these proteins antigentic markers of GBS serotypes to the virulence of the organism and pathogenesis of disease is suggested by in vitro and in vivo findings. The interaction of strains bearing the protein antigens with phagocytic cells and antibody will be pursued by a number of integrated approaches to further our understanding of host responses to these GBS constituents. These surface localized protein antigens may account for variation in the biological behavior of GBS and strain- to-strain variation. The specific research goals are: (1) to pursue further purification and characterization of the c protein, including the IgA binding protein; (2) to study characteristics of IgA binding in GBS strains of major serotypes bearing the c proteins; (3) to pursue the in vitro and in vivo biological activity of polyclonal rabbit antisera to the TR and TS proteins; (4) to characterize further the IgG1 monoclonal antibodies that we have produced to the TR and TS proteins; (5) to produce additional mouse monoclonal antibodies against the TR and TS proteins; (6) to study the presence of antibodies against the TR and TS antigens in the sera of mothers and newborn infants and other adults infected or colonized with group B streptococci; (7) to study the immunogenicity of the TR and TS antigens and their capacity to confer immunological protection by immunization; (8) to study mechanisms of resistance to killing of strains bearing the TR and TS antigens; (9) to pursue studies on the role of R proteins and their role in immunity to GBS. Future projection of these studies includes consideration of these proteins as immunogens that may enhance the immunogenicity of GBS polysaccharide type antigens and thereby be included in vaccine development. In addition, since antibodies against these proteins may confer protection directly, they could contribute to preventive and therapeutic strategies for GBS disease in infants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013926-15
Application #
2060026
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1977-07-01
Project End
1996-06-30
Budget Start
1992-07-01
Budget End
1996-06-30
Support Year
15
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Suvorov, A N; Flores, A E; Ferrieri, P (1997) Cloning of the glutamine synthetase gene from group B streptococci. Infect Immun 65:191-6
Fasola, E L; Flores, A E; Ferrieri, P (1996) Immune responses to the R4 protein antigen of group B streptococci and its relationship to other streptococcal R4 proteins. Clin Diagn Lab Immunol 3:321-5
Chmouryguina, I; Suvorov, A; Ferrieri, P et al. (1996) Conservation of the C5a peptidase genes in group A and B streptococci. Infect Immun 64:2387-90
Flores, A E; Nelson, J A; Wu, X Y et al. (1993) Antibody profiles to the group B streptococcal beta antigen in maternal and infant paired sera. APMIS 101:41-9
Cleary, P P; Handley, J; Suvorov, A N et al. (1992) Similarity between the group B and A streptococcal C5a peptidase genes. Infect Immun 60:4239-44
Belani, K; Schlievert, P M; Kaplan, E L et al. (1991) Association of exotoxin-producing group A streptococci and severe disease in children. Pediatr Infect Dis J 10:351-4
Ferrieri, P (1990) Neonatal susceptibility and immunity to major bacterial pathogens. Rev Infect Dis 12 Suppl 4:S394-400
Flores, A E; Ferrieri, P (1989) Molecular species of R-protein antigens produced by clinical isolates of group B streptococci. J Clin Microbiol 27:1050-4
Ferrieri, P (1988) Surface-localized protein antigens of group B streptococci. Rev Infect Dis 10 Suppl 2:S363-6
Halperin, S A; Ferrieri, P; Gray, E D et al. (1987) Antibody response to bacteriophage hyaluronidase in acute glomerulonephritis after group A streptococcal infection. J Infect Dis 155:253-61

Showing the most recent 10 out of 18 publications