Development of the Sm14/GLA-SE Schistosomiasis Vaccine Candidate: An Open, Non-Placebo-Controlled, Standardized-Dose Immunization Phase Ib Clinical Trial Targeting Healthy Young Women

Abstract

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.

Keywords: Sm14 protein; phase Ib clinical trial; pregnant rabbits; schistosomiasis; toxicology; vaccine.

Figure 1

Normal macroscopic and microscopic views of an ovary from an Sm14/GLA-SE-vaccinated pregnant rabbit. Panel (A) depicts the normal macroscopic pattern of the ovary, showing a multinodular outer surface and brownish structure with marked vessels. Panel (B) shows a microscopic view of follicles in various stages of development in the cortical region (within the black circles). Corpora lutea (CL) can be seen in panel (C), whereas a higher magnification of a follicle can be seen in panel (D). Sections were stained with hematoxylin–eosin. Scale magnification with 40× (in panel (B)), 100× (in panel (C)), and 200× (in panel (D)) objectives.

Figure 2

Total anti-Sm14 IgG antibody titers, determined by ELISA, of all rabbit serum samples from the two groups in the reproductive toxicity study. OD: optical density.

Figure 3

Levels of anti-Sm14 antibody classes and cytokine production stimulated by vaccination. (A) ELISA antibody results. (B) Percentage of CD4⁺ T cells expressing combinations of IFNγ, TNF_α, and IL-2 production in CD4+ T cells on days 0, 30, 90, and 120. The comparison of p-values to baseline was performed for the vaccinated group (day 0); * p-values at the 0.05 significance level.