Development of the Sm14/GLA-SE - schistosomiasis vaccine candidate: An open, not placebo-controlled, standardized dose immunization phase Ib clinical trial targeting healthy young women

We report the successful closure of Phase I clinical trials of the Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) + glucopyranosyl lipid A in squalene emulsion (GLA-SE) vaccine candidate against human Schistosomiasis, comprising Phases Ia and Ib. Shown here are the results of Phase Ib, an open, not placebo-controlled, standardized-dose immunization trial, involving 10 healthy 18-49 years old women submitted to the same clinical protocol and the same batch of cGMP Sm14+GLA-SE used in Phase Ia, which was one on men. Fifty µg Sm14 protein plus 10 µg GLA-SE per dose were 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 feature either in offspring or mothers, as ascertained by histopathology and biochemical parameters. The vaccine induced adaptive immunity in the animals, as defined by the detection of anti-Sm14 antibodies in the sera. In women, neither serious nor light adverse events were observed. Sm14+GLA-SE vaccination induced high titers of anti-Sm14 serum IgG antibody production. Total anti-IgG serum levels remained high 120 days after the first vaccination dose. Significant increases in Sm14-specific total IgG, IgG1, and IgG3 were observed 30 days after the first vaccination, with specific IgG2 and IgG4 after 60 days. Sm14+GLA-SE vaccination also elicited robust cytokine responses with increased TNFα, IFNγ, and IL-2 profiles in all female vaccinees on days 90 and 120. As in Phase Ia, the Sm14+GLA-SE vaccine was shown to be strongly immunogenic and well tolerated. The completion of Phase I clinical trials performed to the highest standards set by the Good Clinical Research Practice (GCP) standards and pre-clinical data in pregnant rabbits enabled the vaccine candidate to proceed to Phase II clinical trials in endemic areas. Study registration ID NCT01154049 at http://www.clinicaltrials.gov . Brazilian Registry of Clinical Trials UTN: U1111-1135-6815