Maternal immunization of mice with group B streptococcal type III polysaccharide-beta C protein conjugate elicits protective antibody to multiple serotypes.

Group B streptococcal infection is a major cause of neonatal mortality. Antibody to the capsular polysaccharide protects against invasive neonatal disease, but immunization with capsular polysaccharides fails to elicit protective antibody in many recipients. Conjugation of the polysaccharide to tetanus toxoid has been shown to increase immune response to the polysaccharide. In animal models, C proteins of group B streptococci are also protective determinants. We examined the ability of the beta C protein to serve in the dual role of carrier for the polysaccharide and protective immunogen. Type III polysaccharide was covalently coupled to beta C protein by reductive amination. Immunization of rabbits with the polysaccharide-protein conjugate elicited high titers of antibody to both components, and the serum induced opsonophagocytic killing of type III, Ia/C, and Ib/C strains of group B streptococci. Female mice were immunized with the conjugate vaccine and then bred; 93% of neonatal pups born to these dams vaccinated with conjugate survived type III group B streptococcal challenge and 76% survived type Ia/C challenge, compared with 3% and 8% survival, respectively, in controls (P < 0.001). The beta C protein acted as an effective carrier for the type III polysaccharide while simultaneously induced protective immunity against beta C protein--containing strains of group B streptococci.

[1]  A. Schuchat,et al.  A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults. , 1993, The New England journal of medicine.

[2]  G. Lindahl,et al.  Protein rib: a novel group B streptococcal cell surface protein that confers protective immunity and is expressed by most strains causing invasive infections , 1993, The Journal of experimental medicine.

[3]  K. Edwards,et al.  Responses of children to booster immunization with their primary conjugate Haemophilus influenzae type B vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid. , 1993, The Journal of pediatrics.

[4]  T. Barington,et al.  Non-epitope-specific suppression of the antibody response to Haemophilus influenzae type b conjugate vaccines by preimmunization with vaccine components , 1993, Infection and immunity.

[5]  D. Kasper,et al.  Group B Streptococcus type II polysaccharide-tetanus toxoid conjugate vaccine , 1992, Infection and immunity.

[6]  D. Kasper,et al.  Phenotypic diversity in the alpha C protein of group B streptococci , 1991, Infection and immunity.

[7]  G. Lindahl,et al.  Molecular characterization of an IgA receptor from group B streptococci: sequence of the gene, identification of a proline‐rich region with unique structure and isolation of N‐terminal fragments with IgA‐binding capacity , 1991, European journal of immunology.

[8]  D. Kasper,et al.  A monoclonal antibody identifies a protective C-protein alpha-antigen epitope in group B streptococci , 1991, Infection and immunity.

[9]  D. Kasper,et al.  An oligosaccharide-tetanus toxoid conjugate vaccine against type III group B Streptococcus. , 1990, The Journal of biological chemistry.

[10]  G. Lindahl,et al.  Characterization of an IgA receptor from group B streptococci: specificity for serum IgA , 1990, European journal of immunology.

[11]  D. Kasper,et al.  Response to type III polysaccharide in women whose infants have had invasive group B streptococcal infection. , 1990, The New England journal of medicine.

[12]  N. Payne,et al.  Nonimmune binding of human immunoglobulin A to type II group B streptococci , 1990, Infection and immunity.

[13]  J. Shiloach,et al.  Synthesis and immunological properties of conjugates composed of group B streptococcus type III capsular polysaccharide covalently bound to tetanus toxoid , 1990, Infection and immunity.

[14]  D. Kasper,et al.  Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus. , 1989, The New England journal of medicine.

[15]  C. Leclerc,et al.  Epitopic suppression in synthetic vaccine models: analysis of the effector mechanisms. , 1987, Cellular immunology.

[16]  L. Bevanger,et al.  Mouse-protective antibodies against the Ibc proteins of group B streptococci. , 2009, Acta pathologica, microbiologica, et immunologica Scandinavica. Section B, Microbiology.

[17]  C. Leclerc,et al.  Carrier-induced epitopic suppression, a major issue for future synthetic vaccines. , 1985, Journal of immunology.

[18]  D. Kasper,et al.  Vaccination as a measure for prevention of neonatal GBS infection. , 1985, Antibiotics and chemotherapy.

[19]  E. Gotschlich,et al.  A surface receptor specific for human IgA on group B streptococci possessing the Ibc protein antigen , 1984, The Journal of experimental medicine.

[20]  Dwight R. Johnson,et al.  Group B streptococcal Ibc protein antigen: distribution of two determinants in wild-type strains of common serotypes , 1984, Journal of clinical microbiology.

[21]  P. Christensen,et al.  Correlation between low levels of maternal IgG antibodies to R protein and neonatal septicemia with group B streptococci carrying R protein. , 1983, International archives of allergy and applied immunology.

[22]  C. Lugowski,et al.  Immunochemistry of groups A, B, and C meningococcal polysaccharide-tetanus toxoid conjugates. , 1981, Journal of immunology.

[23]  D. Kasper,et al.  Influence of preimmunization antibody levels on the specificity of the immune response to related polysaccharide antigens. , 1980, The New England journal of medicine.

[24]  D. Kasper,et al.  Immunochemical characterization of native polysaccharides from group B streptococcus: the relationship of the type III and group B determinants. , 1978, Journal of immunology.

[25]  G. Gray,et al.  Proteins containing reductively aminated disaccharides. Synthesis and chemical characterization. , 1977, Archives of biochemistry and biophysics.

[26]  D. Kasper,et al.  Antigenic specificity of opsonophagocytic antibodies in rabbit anti-sera to group B streptococci. , 1977, Journal of immunology.

[27]  M. Mccarty,et al.  Multiple mouse-protective antibodies directed against group B streptococci. Special reference to antibodies effective against protein antigens , 1975, The Journal of experimental medicine.

[28]  O. Avery,et al.  CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : V. THE IMMUNOLOGICAL SPECIFITY OF AN ANTIGEN PREPARED BY COMBINING THE CAPSULAR POLYSACCHARIDE OF TYPE III PNEUMOCOCCUS WITH FOREIGN PROTEIN , 1931 .