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

Vaccine. 2019 Oct 8;37(43):6500-6509. doi: 10.1016/j.vaccine.2019.08.075. Epub 2019 Sep 9.


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 18-50 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.

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 (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).

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.

Keywords: Adjuvant; Glucopyranosyl lipid A; Immune responses; Immunization; Schistosoma mansoni (Sm); Schistosomiasis; Sm tetraspanin 2 (Sm-TSP-2).

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adolescent
  • Adult
  • Animals
  • Antibodies, Helminth / blood*
  • Antigens, Helminth / immunology
  • Cohort Studies
  • Cytokines / immunology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glucosides / immunology*
  • Healthy Volunteers
  • Humans
  • Immunogenicity, Vaccine*
  • Immunoglobulin G / blood
  • Lipid A / immunology*
  • Male
  • Middle Aged
  • Schistosoma mansoni
  • Schistosomiasis / prevention & control*
  • Vaccines / adverse effects
  • Vaccines / immunology*
  • Young Adult


  • Adjuvants, Immunologic
  • Antibodies, Helminth
  • Antigens, Helminth
  • Cytokines
  • Glucosides
  • Immunoglobulin G
  • Lipid A
  • Vaccines
  • glucopyranosyl lipid-A