Safety and Immunogenicity of a Novel Staphylococcus aureus Vaccine: Results from the First Study of the Vaccine Dose Range in Humans

Merck V710 is a novel vaccine containing the conserved Staphylococcus aureus iron surface determinant B shown to be protective in animal models. A phase I, multicenter, double-blind study of the dose range was conducted to assess the immunogenicity and safety of an adjuvanted liquid formulation of V710. A total of 124 adults (18 to 55 years of age) were randomized 1:1:1:1 to receive one 0.5-ml intramuscular injection of V710 (5 mu g, 30 mu g, or 90 mu g) or saline placebo. A positive immune response was defined as at least a 2-fold increase in IsdB-specific IgG levels from baseline levels. Local and systemic adverse events were assessed for 5 and 14 days, respectively, following vaccination. Positive immune responses were detected in 12 (67%) of the 18 subjects in the groups receiving 30 and 90 mu g V710 tested at day 10. At day 14, a significantly greater proportion of subjects manifested a positive immune response with higher geometric mean concentrations in the V710 30-mu g (86%; geometric mean concentration of 116 mu g/ml) and 90-mu g (87%; geometric mean concentration of 131 mu g/ml) dose groups than in the V710 5-mu g (29%; geometric mean concentration of 51 mu g/ml) or placebo (4%; geometric mean concentration of 23 mu g/ml) groups. Immune responses were durable through day 84. Subjects <40 and >= 40 years of age had comparable immune responses. The most common adverse events were injection-site pain, nausea, fatigue, and headache, usually of mild intensity. No immediate reactions or serious adverse events were reported. In this first study of V710 in humans, a single 30-mu g or 90-mu g dose was more immunogenic than the 5-mu g dose or placebo. Immune responses were evident by 10 to 14 days after vaccination in most responders.