title: Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: Phase III randomized study.
abstract: In a previous study in end-stage renal disease (ESRD) hemodialysis patients, a single dose of Staphylococcus aureus type 5 and 8 capsular polysaccharides (T5/T8) conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A investigational vaccine showed no efficacy against S. aureus bacteremia 1 year post-vaccination, but a trend for efficacy was observed over the first 40 weeks post-vaccination. Vaccine efficacy (VE) of 2 vaccine doses was therefore evaluated. In a double-blind trial 3359 ESRD patients were randomized (1:1) to receive vaccine or placebo at week 0 and 35. VE in preventing S. aureus bacteremia was assessed between 3-35 weeks and 3-60 weeks post-dose-1. Anti-T5 and anti-T8 antibodies were measured. Serious adverse events (SAEs) were recorded for 42 days post-vaccination and deaths until study end. No significant difference in the incidence of S. aureus bacteremia was observed between vaccine and placebo groups between weeks 3-35 weeks post-dose 1 (VE -23%, 95%CI: -98;23, p = 0.39) or at 3-60 weeks post-dose-1 (VE -8%, 95%CI: -57;26, p = 0.70). Day 42 geometric mean antibody concentrations were 272.4 μg/ml and 242.0 μg/ml (T5 and T8, respectively) in vaccinees. SAEs were reported by 24%/25.3% of vaccinees/placebo recipients. These data do not show a protective effect of either 1 or 2 vaccine doses against S. aureus bacteremia in ESRD patients. The vaccine induced a robust immune response and had an acceptable safety profile. Further investigation suggested possible suboptimal vaccine quality (manufacturing) and a need to expand the antigen composition of the vaccine. This study is registered at www.clinicaltrials.gov NCT00071214.
authors.affiliation: a Nabi Biopharmaceuticals ; Rockville , MD USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Fattom
authors.forename: Albert
authors.initials: A
authors.lastname: Matalon
authors.forename: John
authors.initials: J
authors.lastname: Buerkert
authors.forename: Kimberly
authors.initials: K
authors.lastname: Taylor
authors.forename: Silvia
authors.initials: S
authors.lastname: Damaso
authors.forename: Dominique
authors.initials: D
authors.lastname: Boutriau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D016470:Bacteremia / Q000276:immunology / Q000517:prevention & control*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects*; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D016896:Treatment Outcome; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D010919:Placebos; D013209:Staphylococcal Vaccines; D018074:Vaccines, Conjugate
keywords: CI, confidence interval; ClfA, S. aureus clumping factor A; ELISA, enzyme-linked immunosorbent assay; ESRD, end-stage renal disease; GMC, geometric mean concentration; OPK, opsonophagocytic killing; SAE, Serious adverse event; Staphylococcus aureus; T5/T8, Staphylococcus aureus type 5 and 8 capsular polysaccharides; VE, vaccine efficacy; end stage renal disease; hemodialysis; immunogenicity; vaccine; vaccine safety