Human vaccines & immunotherapeutics
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Hum Vaccin Immunother · Jan 2014
Randomized Controlled Trial Multicenter StudyPhase IV: randomized controlled trial to evaluate lot consistency of trivalent split influenza vaccines in healthy adults.
Influenza vaccines are the primary method for preventing influenza and its complications. Considering the increasing demand for influenza vaccines, vaccine manufacturers are required to establish large-scale production systems. This phase IV randomized trial was conducted to evaluate the lot consistency of trivalent split influenza vaccines regarding immunogenicity and safety. ⋯ After vaccination, all 3 criteria of the European Medicines Agency were met in both GC FLU® Injection and GC FLU® Prefilled Syringe groups. The vaccines showed tolerable safety profiles without serious adverse events. The demonstration of lot consistency, robust immunogenic responses and favorable safety profiles support the reliability of mass-manufacturing systems for the GC FLU® Injection and GC FLU® Prefilled Syringe.
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Hum Vaccin Immunother · Jan 2014
Randomized Controlled Trial Multicenter StudySustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination.
HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15-25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). ⋯ All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine.
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Hum Vaccin Immunother · Jan 2014
Randomized Controlled Trial Multicenter Study Observational StudyA randomized, placebo-controlled phase I study assessing the safety and immunogenicity of a Pseudomonas aeruginosa hybrid outer membrane protein OprF/I vaccine (IC43) in healthy volunteers.
IC43 is a recombinant outer membrane protein-based vaccine against Pseudomonas aeruginosa (P. aeruginosa) consisting of OprF- and OprI- epitopes (Opr, outer membrane protein; OprF/I, OprF/OprI hybrid vaccine) with an N-terminal His 6 tag (Met-Ala-(His)6-OprF190-342-OprI21-83). ⋯ In this phase I, randomized, placebo-controlled, observer-blinded, multicenter clinical trial, 163 healthy volunteers (18-65 y) were randomly assigned to five treatment groups (1:1:1:1:1). Three groups received IC43 with adjuvant: 50 µg (n=32), 100 µg (n=33), or 200 µg (n=33). One group received IC43 100 µg without adjuvant (n=32), and one group received placebo (0.9% sodium chloride) (n=33). Each subject received two intramuscular vaccinations, separated by a 7-d interval (days 0 and 7) (Fig. 1). Humoral immune response was assessed by measurement of outer membrane protein F/I (OprF/I)-specific antibodies determined by enzyme-linked immunosorbent assay (ELISA), anti-histidine antibodies determined by ELISA, and functional antibody activity determined by opsonophagocytic assay (OPA), up to 6 mo post-vaccination. Antibody avidity was measured on days 7 and 14 from samples that had detectable vaccine antibody-specific immunoglobulin G (IgG) antibody titers. At the Austrian site only, the B-cell ELIspot assay was used to determine specific ASC responses. Safety was assessed using adverse event monitoring and clinical laboratory tests. Local and systemic tolerability was recorded in a subject diary for 7 d after each vaccination and by investigators up to 6 mo post-vaccination.
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Hum Vaccin Immunother · Jan 2014
Randomized Controlled Trial Multicenter StudyA dose-ranging study of MF59(®)-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination.
During development of an A/H1N1 pandemic influenza vaccine, this study was performed to identify the antigen and adjuvant content which would provide optimal antibody response and persistence in adults and the elderly. Dose-sparing strategies, such as inclusion of adjuvants, are critical in ensuring the widest possible population coverage in the event of an influenza pandemic, despite a limited global capacity for vaccine manufacture. ⋯ A single vaccine dose containing 3.75 µg of A/California/7/2009 (H1N1) antigen with MF59 adjuvant was identified as optimal for young to middle-aged (18-64 years) and older (≥65 years) adult populations.
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Hum Vaccin Immunother · Jan 2014
Multicenter Study Clinical TrialSafety of AS03-adjuvanted inactivated split virion A(H1N1)pdm09 and H5N1 influenza virus vaccines administered to adults: pooled analysis of 28 clinical trials.
Clinical trials have shown that AS03-adjuvanted H5N1 and A(H1N1)pdm09 vaccines are highly immunogenic, although with an increased reactogenicity profile relative to non-adjuvanted vaccines in terms of the incidence of common injection site and systemic adverse events (AEs). We evaluated pooled safety data from 22,521 adults who had received an AS03-adjuvanted H5N1 or A(H1N1)pdm09 influenza or control vaccine with the purpose to identify medically-attended AEs (MAEs), including subsets of serious AEs (SAEs), potentially immune-mediated diseases (pIMDs), and AEs of special interest (AESI), and to explore a potential association of these AEs with the administration of an AS03-adjuvanted influenza vaccine. For participants who had received an AS03-adjuvanted vaccine, the relative risks (RRs) for experiencing a MAE or a SAE compared to control group (participants who had received a non-adjuvanted vaccine or saline placebo) were 1.0 (95% confidence interval [CI]: 0.9; 1.1) and 1.1 (95% CI: 0.9; 1.4), respectively. ⋯ Thirty-8 participants in the AS03-adjuvanted vaccine group had a pIMD reported after vaccine administration, yielding an incidence rate (IR) of 351.9 (95% CI: 249.1; 483.1) per 100,000 person-years. The estimated IRs in the AS03-adjuvanted vaccine group were greater than the literature reported rates for: facial paresis/VIIth nerve paralysis, celiac disease, thrombocytopenia and ulcerative colitis. These results do not support an association between AS03-adjuvanted H5N1 and A(H1N1)pdm09 vaccines and the AEs collected in the trials included in the analysis.