title: Functional activity of antisera to group B streptococcal conjugate vaccines measured with an opsonophagocytosis assay and HL-60 effector cells.
abstract: Conjugate vaccines against group B Streptococcus (GBS), which is a leading cause of bacterial disease among newborns and the elderly with underlying illnesses, have progressed from animal studies to phase 1 and 2 clinical trials in healthy adults. Due to the wide-spread use of antibiotics to treat at-risk deliveries, a phase 3 efficacy trial of a GBS vaccine to prevent neonatal disease in the United States is unlikely. A viable approach to assess a vaccine's efficacy is to use a surrogate of protection which in the case of GBS is the opsonizing activity of serum antibody. The opsonophagocytosis assay (OPA) measures the ability of serum antibody to opsonize GBS for killing by effector cells in the presence of complement. In this report we demonstrate that differentiated HL-60 cells can substitute for human peripheral blood leukocytes (hPMNLs) in the OPA. Antisera to GBS type Ia CPS and type III CPS conjugate vaccines opsonized homologous GBS for killing at effector cells to GBS ratios of 2-4:1 regardless of whether HL-60 or hPMNLs were used. These results represent the first important step in developing a standardized, high-throughput OPA that could be used to assess the functional activity of vaccine-induced antibody and potentially serve as a surrogate of efficacy.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. lpaoletti@rics.bwh.harvard.edu
authors.forename: Hilde-Kari
authors.initials: HK
authors.lastname: Guttormsen
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Liu
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Paoletti
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000276:immunology; D015415:Biomarkers; D045744:Cell Line, Tumor; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D007118:Immunoassay / Q000379:methods; D009895:Opsonin Proteins / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D011817:Rabbits; D022541:Streptococcal Vaccines / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D015415:Biomarkers; D007106:Immune Sera; D009895:Opsonin Proteins; D022541:Streptococcal Vaccines; D018074:Vaccines, Conjugate; C105866:group B streptococcal type III capsular polysaccharide-tetanus toxoid vaccine; C105864:group B streptococcal type Ia capsular polysaccharide-tetanus toxoid vaccine