Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03Badjuvant: Results of a randomized phase I trial
| Autor: | Edwige Haelterman, Philippe Moris, Laurent Licini, Jack Levy, Dominique Boutriau, Pascale Van Belle, Silvia Damaso, Pascal Lestrate |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Squalene safety Staphylococcus aureus Adolescent Drug-Related Side Effects and Adverse Reactions medicine.medical_treatment alpha-Tocopherol Immunology Polysorbates CD8-Positive T-Lymphocytes immunogenicity Placebos Young Adult Adjuvants Immunologic adjuvant Immunity vaccine medicine Humans Immunology and Allergy Single-Blind Method Adverse effect Pharmacology Reactogenicity Tetanus business.industry Immunogenicity Toxoid Staphylococcal Vaccines Staphylococcal Infections medicine.disease Antibodies Bacterial Healthy Volunteers Clumping factor A Drug Combinations Female business Adjuvant Research Paper |
| Zdroj: | Human Vaccines & Immunotherapeutics |
| ISSN: | 2164-554X 2164-5515 |
| DOI: | 10.1080/21645515.2015.1011021 |
| Popis: | We assessed the safety, reactogenicity and immunogenicity of a staphylococcal vaccine combining capsular polysaccharides types 5 and 8 (CPS5/8), conjugated to tetanus toxoid (TT), with mutated detoxified α-toxin (AT) and clumping factor A (ClfA). In this phase I, randomized, placebo-controlled, observer-blind trial (NCT01160172), 88 healthy 18- to 40-year-olds received CPS5-TT/CPS8-TT/AT/ClfA vaccine (5/5/10/10 μg or 10/10/30/30 μg dose, each with or without AS03B adjuvant) or saline, at months 0, 1, 6. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 d post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) were recorded throughout the study. Humoral and antigen-specific CD4(+)/CD8(+) T-cell immunity were assessed from Day (D) 0 to D540 post-vaccination. The most frequently reported solicited local and general AEs were pain (78.6%-100% of subjects), fatigue (36.4%-93.3% of subjects post-dose 1-2) and headache (20%-44.4% of subjects post-dose 3). Overall, 4 SAEs and 2 potential immune-mediated diseases (pIMDs) (none fatal or vaccine-related) were reported. For each antigen, pre-vaccination seropositivity rates were high (85.7%-100%) and geometric mean concentrations (GMCs) in vaccine recipients sharply increased from D0 to D14, then plateaued to study end. Exploratory group comparisons suggested higher GMCs with higher dosage, without AS03B effect. Vaccine-induced antibodies were functional (CPS5 opsonophagocytic assays, and AT/ClfA inhibition assays). AT- and ClfA-specific CD4(+) T-cells with Th0/Th1 cytokine profile were induced at low levels (median |
| Databáze: | OpenAIRE |
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