A phase 1 study of the safety, reactogenicity, and immunogenicity of a Schistosoma mansoni vaccine with or without glucopyranosyl lipid A aqueous formulation (GLA-AF) in healthy adults from a non-endemic area

Abstract

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. 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 18–50 year olds were randomized to receive 3 doses~ 8 weeks apart of saline placebo, or 10 μg, 30 μg, or 100 μg of recombinant Sm -Tetraspanin-2 vaccine formulated on aluminum hydroxide adjuvant ( Sm -TSP-2/Al) with or without 5 μg of glucopyranosyl lipid A aqueous formulation (GLA-AF). Clinical and serologic responses were assessed for 1 year after dose 3. 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 (p = 0.0036 and p = 0.0014, respectively). Injection site reactions among those given Sm -TSP-2/Al with GLA-AF lasted 1.22 and 1.33 days longer than those receiving Sm -TSP-2/Al without GLA-AF or placebo (p < 0.001 for both). Dose- and adjuvant-related increases in serum IgG against Sm -TSP-2 were observed. Peak IgG levels occurred 14 days after dose 3. Seroresponse frequencies were low among recipients of Sm -TSP-2/Al without GLA-AF, but higher among subjects receiving 30 μg or 100 μg of Sm -TSP-2/Al with GLA-AF. More seroresponses were observed among those given 30 μg or 100 μg of Sm -TSP-2/Al with GLA-AF compared to placebo (p = 0.023 and p < 0.001, respectively). Seroresponse frequencies were 0%, 30%, 50%, and 89%, respectively, among those given placebo, or 10 μg, 30 μg or 100 μg of Sm -TSP-2/Al with GLA-AF, suggesting a dose-response relationship for Sm -TSP-2/Al with GLA-AF (p = 0.0001). 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.