title: Recombinant group B streptococcus Beta C protein and a variant with the deletion of its immunoglobulin A-binding site are protective mouse maternal vaccines and effective carriers in conjugate vaccines.
abstract: Immunogenic vaccines against group B Streptococcus (GBS) have been created by coupling the GBS capsular polysaccharides (CPS) to carrier proteins. The GBS beta C protein (BCP) serves as an effective carrier while inducing protective immunity against BCP-expressing strains. BCP also binds human immunoglobulin A (IgA), a characteristic that may be undesirable for use in humans. Here, we examined the immunogenicity and protective efficacy of a recombinant GBS BCP (rBCP), an rBCP modified to eliminate its IgA-binding site (rBCP(DeltaIgA)), and their corresponding GBS serotype III CPS conjugates (III-rBCP and III-rBCP(DeltaIgA)). Deletion of the IgA-binding site or conjugation to CPS did not alter antigenic BCP epitopes. Recombinant proteins and conjugates elicited specific, high-titered IgG in mice. Antisera to rBCP, rBCP(DeltaIgA), III-rBCP, and III-rBCP(DeltaIgA) opsonized GBS strains A909 (Ia/BCP(+)) and H36B (Ib/BCP(+)) for killing by HL-60 cells; antiserum to III-rBCP and III-rBCP(DeltaIgA) also opsonized strain M781 (III/BCP(-)). Vaccination of female mice with either rBCP or rBCP(DeltaIgA) protected approximately 40% of their pups challenged with GBS strain A909. Pups born to III-rBCP- or III-rBCP(DeltaIgA)-vaccinated dams survived at rates of 56% and 66%, respectively. Over 90% of pups born to dams that received the type III CPS conjugates survived challenge with GBS strain M781. In summary, rBCP and rBCP(DeltaIgA) proteins and the conjugates containing them were immunogenic in mice, inducing both CPS- and protein-specific functional IgG. These results suggest that the rBCP(DeltaIgA) could be used as a carrier to augment the immunogenicity of the CPS while expanding coverage to GBS strains bearing BCP.
authors.affiliation: Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Yang
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Madoff
authors.forename: Hilde-Kari
authors.initials: HK
authors.lastname: Guttormsen
authors.forename: Yong-Dong
authors.initials: YD
authors.lastname: Liu
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Paoletti
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D021461:Animals, Outbred Strains; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016667:Bacterial Capsules / Q000276:immunology; D001665:Binding Sites / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D018922:HL-60 Cells; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D022541:Streptococcal Vaccines; D018074:Vaccines, Conjugate; C070010:streptococcal beta antigen