title: A randomized, observer-blind Phase Ib study to identify formulations and vaccine schedules of a trivalent Group B Streptococcus vaccine for use in non-pregnant and pregnant women.
abstract: BACKGROUND
  Group B streptococcus (GBS) is a leading cause of sepsis and meningitis in early infancy. Substantial data demonstrate that women with higher levels of circulating antibody against the capsular polysaccharide (CPS) deliver infants at reduced risk of GBS infection, which serves as the basis for vaccine design. This study evaluates two different dosages, two injection schedules and three formulations of an investigational trivalent (serotypes Ia, Ib and III) CRM197-glycoconjugate GBS vaccine in healthy, non-pregnant women.
  
  
  METHODS
  678 healthy non-pregnant women received one or two injections of one of two dosages (5/5/5 μg or 20/20/20 μg) of the investigational vaccine, formulated with or without aluminum hydroxide (Enrollment Group 1), or with full or half dosages of MF59(®) (Enrollment Group 2); or a placebo (Enrollment Groups 1 and 2). Geometric mean serotype-specific antibody concentrations (GMCs) at Days 61 (Enrollment Group 1) and 361 (both Groups) were analyzed to select a formulation suitable for pregnant or non-pregnant women, respectively. Solicited adverse reactions were recorded up to Day 7 and adverse events (AEs) were recorded throughout the study.
  
  
  RESULTS
  Rates of reported AEs were similar across all groups. Higher rates of local reactogenicity were seen in adjuvanted vaccine groups compared with non-adjuvanted vaccine (or placebo) groups. All vaccine groups elicited higher GMCs than placebo; differences between treatments were not statistically significant, indicating no additional potential benefit of higher antigen content, addition of adjuvant, or a second dose.
  
  
  CONCLUSIONS
  All GBS vaccine formulations induced a persistent antibody response and showed similar immunogenicity profiles (NCT01150123).
authors.affiliation: Centre for Vaccinology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: Centre for Vaccinology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Cathy
authors.initials: C
authors.lastname: Maes
authors.affiliation: Centre for Vaccinology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Willekens
authors.affiliation: Centre for Vaccinology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Fien
authors.initials: F
authors.lastname: De Boever
authors.affiliation: GlaxoSmithKline BV, Amsterdam, The Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: de Rooij
authors.affiliation: GlaxoSmithKline LLC, Cambridge, MA, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Martell
authors.affiliation: GlaxoSmithKline LLC, Cambridge, MA, USA. Electronic address: lisa.x.bedell@gsk.com.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bedell
authors.affiliation: GSK Vaccines S.r.l, Siena, Italy.
authors.forename: Frederick
authors.initials: F
authors.lastname: Wittke
authors.affiliation: GlaxoSmithKline LLC, Cambridge, MA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Slobod
authors.affiliation: GlaxoSmithKline LLC, Cambridge, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Dull
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007115:Immunization Schedule; D011135:Polysaccharides, Bacterial / Q000276:immunology; D011247:Pregnancy; D016037:Single-Blind Method; D013290:Streptococcal Infections / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013292:Streptococcus agalactiae; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D011135:Polysaccharides, Bacterial; D022541:Streptococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Adjuvant; Group B streptococcus; Trivalent vaccine