Immunogenicity and safety of a tetravalent E. coli O-antigen bioconjugate vaccine in animal models.

BACKGROUND: Extra-intestinal pathogenic Escherichia coli (ExPEC) are major human pathogens; however, no protective vaccine is currently available. We assessed in animal models the immunogenicity and safety of a 4-valent E. coli conjugate vaccine (ExPEC-4V, serotypes O1, O2, O6 and O25 conjugated to Exotoxin A from Pseudomonas aeruginosa (EPA)) produced using a novel in vivo bioconjugation method. METHODS: Three doses of ExPEC-4V (with or without aluminum hydroxide) were administered to rabbits (2µg or 20µg per O-antigen, subcutaneously), mice (0.2µg or 2µg per O-antigen, subcutaneously) and rats (0.4µg or 4µg per O-antigen, intramuscularly). Antibody persistence and boostability were evaluated in rats using O6-EPA monovalent conjugate (0.4µg O-antigen/dose, intramuscularly). Toxicity was assessed in rats (16µg total polysaccharide, intramuscularly). Serum IgG and IgM antibodies were measured by ELISA. RESULTS: Robust antigen-specific IgG responses were observed in all animal models, with increased responses in rabbits when administered with adjuvant. O antigen-specific antibody responses persisted up to 168days post-priming. Booster immunization induced a rapid recall response. Toxicity of ExPEC-4V when administered to rats was considered to be at the no observed adverse effect level. CONCLUSIONS: ExPEC-4V conjugate vaccine showed good immunogenicity and tolerability in animal models supporting progression to clinical evaluation.

The use of bilateral sacral nerve stimulation in patients with loss of unilateral treatment efficacy.

PURPOSE: We evaluated whether bilateral sacral nerve stimulation can be effective to restore treatment efficacy in patients in whom unilateral sacral neuromodulation fails. MATERIALS AND METHODS: Patients in whom unilateral sacral neuromodulation failed were included in analysis. The percutaneous nerve evaluation test was used to evaluate the effect of contralateral and bilateral stimulation. The stimulation electrode was placed in the contralateral S3 foramen and symptoms were self-recorded using a 3-day voiding diary. Clinical success was defined as more than 50% improvement in at least 1 relevant voiding diary parameter vs baseline. RESULTS: The 15 study patients underwent test stimulation with percutaneous nerve evaluation. In 3 patients lead migration was suspected and, thus, they were not included in analysis. Four of the remaining 12 patients had a successful response to percutaneous nerve evaluation, of whom 3 were eventually implanted with a contralateral lead. After 12 months of treatment 2 of the 3 patients had a successful outcome. CONCLUSIONS: In this pilot study only a select group of patients appeared to benefit from bilateral stimulation after unilateral therapy failure. Further investigation is needed to determine the predictive factors and cost-effectiveness of this treatment.

Is the screening method of sacral neuromodulation a prognostic factor for long-term success?

PURPOSE: We evaluated whether there is a difference in long-term outcomes between patients screened with percutaneous nerve evaluation and a first stage tined lead procedure. We also evaluated the outcome in patients who only responded to screening with the tined lead procedure after failed initial percutaneous nerve evaluation. MATERIALS AND METHODS: We evaluated all patients screened for eligibility to receive sacral neuromodulation treatment since the introduction of the tined lead technique in our center in 2002. In May 2009 all implanted patients were asked to maintain a voiding diary to record the effect of sacral neuromodulation on urinary symptoms. Chi-square analysis was used to evaluate differences in the long-term outcomes of the separate screening methods. RESULTS: A total of 92 patients were screened for sacral neuromodulation. Of the 76 patients screened with percutaneous nerve evaluation 35 (46%) met the criteria for permanent implantation. In 11 of the 16 patients (69%) who underwent direct screening with the tined lead procedure permanent stimulators were placed. Of the 41 patients in whom percutaneous nerve evaluation failed and who subsequently underwent screening with tined lead procedure 18 (44%) were implanted with a neurostimulator after a successful response. Statistical analysis showed no difference between screening type and long-term success (p = 0.94). CONCLUSIONS: The first stage tined lead procedure is a more sensitive screening tool than percutaneous nerve evaluation but long-term success seems to be independent of the screening method. Patients in whom percutaneous nerve evaluation initially failed but who responded to prolonged screening the with tined lead procedure appeared to be as successful as those who directly responded to percutaneous nerve evaluation or the tined lead procedure.