RESUMO
BACKGROUND: Schistosomiasis caused by Schistosoma mansoni (Sm) is a chronic, debilitating and potentially deadly neglected tropical disease. The licensure of a vaccine to prevent schistosomiasis would represent a major breakthrough in public health. METHODS: The safety and immunogenicity of a candidate Sm vaccine were assessed in this phase I, double-blind, dose-escalation trial. Seventy-two healthy Sm-naïve 18-50â¯year olds were randomized to receive 3 doses â¼â¯8â¯weeks apart of saline placebo, or 10⯵g, 30⯵g, or 100⯵g of recombinant Sm-Tetraspanin-2 vaccine formulated on aluminum hydroxide adjuvant (Sm-TSP-2/Al) with or without 5⯵g of glucopyranosyl lipid A aqueous formulation (GLA-AF). Clinical and serologic responses were assessed for 1â¯year after dose 3. RESULTS: Vaccines were safe and well-tolerated. The most common reactions were injection site tenderness and pain, and headache and fatigue. Tenderness and pain were more frequent in groups receiving vaccine with GLA-AF than placebo (pâ¯=â¯0.0036 and pâ¯=â¯0.0014, respectively). Injection site reactions among those given Sm-TSP-2/Al with GLA-AF lasted 1.22 and 1.33â¯days longer than those receiving Sm-TSP-2/Al without GLA-AF or placebo (pâ¯<â¯0.001 for both). Dose- and adjuvant-related increases in serum IgG against Sm-TSP-2 were observed. Peak IgG levels occurred 14â¯days after dose 3. Seroresponse frequencies were low among recipients of Sm-TSP-2/Al without GLA-AF, but higher among subjects receiving 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF. More seroresponses were observed among those given 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF compared to placebo (pâ¯=â¯0.023 and pâ¯<â¯0.001, respectively). Seroresponse frequencies were 0%, 30%, 50%, and 89%, respectively, among those given placebo, or 10⯵g, 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF, suggesting a dose-response relationship for Sm-TSP-2/Al with GLA-AF (pâ¯=â¯0.0001). CONCLUSIONS: Sm-TSP-2/Al with or without GLA-AF was safe and well tolerated in a Sm-naïve population. A vaccine like the one under development may represent our best hope to eliminating this neglected tropical disease.