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: Ali Fattom, Albert Matalon, John Buerkert, Kimberly Taylor, Silvia Damaso, Dominique Boutriau
• Journal: Human vaccines & immunotherapeutics (Hum Vaccin Immunother) Vol. 11 Issue 3 Pg. 632-41 ( 2015) ISSN: 2164-554X [Electronic] United States
• PMID: 25483694 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Placebos
• Staphylococcal Vaccines
• Vaccines, Conjugate

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Bacterial (blood)
• Bacteremia (immunology, prevention & control)
• Double-Blind Method
• Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
• Female
• Humans
• Incidence
• Kidney Failure, Chronic (complications, therapy)
• Male
• Middle Aged
• Placebos (administration & dosage)
• Prospective Studies
• Renal Dialysis (adverse effects)
• Staphylococcal Infections (immunology, prevention & control)
• Staphylococcal Vaccines (administration & dosage, adverse effects, immunology)
• Staphylococcus aureus (immunology)
• Treatment Outcome
• Vaccines, Conjugate (administration & dosage, adverse effects, immunology)
• Young Adult