Safety and immunogenicity of an investigational 4-component Staphylococcus aureus vaccine with or without AS03B adjuvant: Results of a randomized phase I trial.

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 <0.05%) by each formulation (intracellular cytokine staining). In conclusion, no safety concerns were identified and each vaccine formulation induced robust humoral immune responses after the first vaccine dose.