Pharmacokinetics and Immunogenicity of ASP0113 in CMV-Seronegative Dialysis Patients and CMV-Seronegative and -Seropositive Healthy Subjects.

Cytomegalovirus (CMV) infection causes significant morbidity and mortality in immunocompromised transplant patients. ASP0113, a first-in-class DNA vaccine containing plasmids encoding CMV phosphoprotein 65 and glycoprotein B (gB), was evaluated in a phase 1b, subject-blinded study in CMV-seropositive (n = 13) and CMV-seronegative (n = 12) healthy and CMV-seronegative dialysis subjects (n = 12) randomized to ASP0113 or placebo. End points included pharmacokinetics, anti-gB antibody levels, phosphoprotein 65-specific T-cell responses measured by ex vivo enzyme-linked immune absorbent spot (ELISpot) assay and 10-day cultured ELISpot and Stat T-cell activation assays, and safety. ASP0113 concentrations peaked at 2-10 and 24-48 hours; the pharmacokinetics were similar across groups. No group demonstrated significant anti-gB antibody responses. T-cell responder rates in the cultured ELISpot assay were 8/12 (66.7%, 95%CI 35% to 90%) and 4/12 (33.3%, 95%CI 10% to 65%) in CMV-seronegative healthy subjects and dialysis patients, respectively, whereas ex vivo ELISpot assay response rates were 4/11 (36.4%, 95%CI 11% to 69%) and 0/12, respectively. Responses peaked at week 27, with lower magnitude observed in CMV-seronegative dialysis patients versus CMV-seronegative healthy subjects. No serious adverse events occurred; the most common adverse event in ASP0113-vaccinated patients was injection-site pain (64.9%). Some CMV-seronegative healthy subjects and dialysis patients had T-cell responses; no humoral responses were detected.

Five-year follow-up of supportive psychodynamic psychotherapy in first-episode psychosis: long-term outcome in social functioning.

OBJECTIVES: The long-term outcomes of several approaches to intervention targeting social functioning in schizophrenia are not well documented. Contemporary supportive psychodynamic psychotherapy (SPP) aims to improve social functioning. The aim of the present study was to investigate the long-term outcome of SPP in a prospective, longitudinal, comparative, multicenter investigation of successively referred patients diagnosed with first-episode schizophrenia spectrum disorder. METHOD: Manualized SPP for up to 3 years as a supplement to standard treatment (ST) were compared to ST alone and followed up for 5 years (N = 269). The SPP targeted interpersonal relationships, emotion regulation, social cognition, and self-coherence. RESULTS: Significant between-group effects in favor of SPP+ST on social functioning, overall symptoms, and positive psychotic symptoms were found during the period of active SPP intervention. These differential effects, however, were not sustained after end of additional SPP at 5-year follow-up. CONCLUSION: The findings are in line with results from other approaches targeting social functioning in schizophrenia and support SPP as a valuable treatment. Further research into the curative elements of SPP is needed.