We report the successful closure of Phase I clinical trials, comprising Phases Ia and Ib, of the vaccine candidate against human schistosomiasis: the Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) + glucopyranosyl lipid A in squalene emulsion (GLA-SE). Shown here are the results of Phase Ib, an open, non-placebo-controlled, standardized-dose immunization trial involving 10 healthy 18–49-year-old women. Fifty micrograms of the Sm14 protein plus 10 µg GLA-SE per dose was given intramuscularly thrice at 30-day intervals. Participants were assessed clinically, biochemically, and immunologically for up to 120 days. In preambular experiments involving vaccinated pregnant female rabbits, we did not find any toxicological features in either the offspring or mothers, and the vaccine induced adaptive immunity in the animals. In women, no adverse events were observed, and vaccination induced high titers of anti-Sm14 serum IgG antibody production. Vaccination also elicited robust cytokine responses, with increased TNFα, IFNγ, and IL-2 profiles in all vaccinees on days 90 and 120. The completion of Phase I clinical trials, which were performed to the highest standards set by Good Clinical Research Practice (GCP) standards, and preclinical data in pregnant rabbits enabled the vaccine candidate to proceed to Phase II clinical trials in endemic areas.

Background/Objectives: Following previous successful Phase I clinical trials conducted in men and women in a non-endemic area for schistosomiasis in Brazil, the Sm14 vaccine was evaluated in an endemic region in Senegal. We report successful clinical trials in adults (Phase IIa) and school children (Phase IIb), respectively, of a Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) vaccine + a glucopyranosyl lipid A (GLA-SE) adjuvant. Methods: Participants were evaluated based on clinical assessments, laboratory tests (including hematologic and biochemical analyses of renal and hepatic functions), and immunological parameters (humoral and cellular responses) up to 12 months after the first vaccination dose in the Phase IIa trial and after 120 days in the Phase IIb trial. Results: The results showed strong immunogenic responses and good tolerance in both adults and children, with no major adverse effects. Importantly, significant increases in Sm14-specific total IgG (IgG1 and IgG3) were observed as early as 30 days after the first vaccination, with high titres remaining at least 120 days afterwards. Sm14-specific total IgG serum levels were also significantly enhanced in adults and in both infected and non-infected, vaccinated children and elicited robust cytokine responses with increased TNFα, IFN-γ, and IL-2 profiles. Conclusions: Overall, the Sm14+GLA-SE vaccine is safe and highly immunogenic, with a clearly protective potential against schistosomiasis, supporting progression to the next Phase III clinical trials.