Abstract
Schistosomiasis threatens 800 million people worldwide. Chronic pathology manifests as hepatosplenomegaly, and intestinal schistosomiasis caused by Schistosoma mansoni can lead to liver fibrosis, cirrhosis, and blood in the stool. To assist the only FDA-approved drug, praziquantel, in parasite elimination, the development of a vaccine would be of high value. S. mansoni Cathepsin B (SmCB) is a well-documented vaccine target for intestinal schistosomiasis. Herein, we test the increased efficacy and immunogenicity of SmCB when combined with sulfated lactosyl archaeol (SLA) archaeosomes or AddaVax™ (a squalene based oil-in-water emulsion). Both vaccine formulations resulted in robust humoral and cell mediated immune responses. Impressively, both formulations were able to reduce parasite burden greater than 40% (WHO standard), with AddaVax™ reaching 86.8%. Additionally, SmCB with both adjuvants were able to reduce granuloma size and the amount of larval parasite hatched from feces, which would reduce transmission. Our data support SmCB as a target for S. mansoni vaccination; especially when used in an adjuvanted formulation.
Highlights
Schistosomiasis (Bilharzia) is an underestimated parasitic disease for which over 800 million people are at risk [1]
No mice had detectable S. mansoni Cathepsin B (SmCB)-specific IgG antibodies at baseline, and the phosphate-buffered saline (PBS) control remained negative throughout the study (Figure 1A)
At week 3, groups adjuvanted with Montanide and AddaVax had significantly higher titers than with sulfated lactosyl archaeol (SLA), this difference was no longer significant post first boost
Summary
Schistosomiasis (Bilharzia) is an underestimated parasitic disease for which over 800 million people are at risk [1]. This blood fluke spreads through fresh water in tropical and sub-tropical regions. Praziquantel (PZQ) used for the treatment of schistosomiasis has a reported efficacy of 86–93% [3, 4]. It does not protect individuals from reinfection or remove pre-existing egg deposition. In the 1990s, independent testing of six candidate S. mansoni antigens underwent protective studies organized by a UNDP/World Bank/ WHO Special Programme for Research and Training in Tropical Diseases (TDR/WHO) committee. These trials resulted in protection, the WHO goal of 40% or greater protection was not met, headlining the need for possible adjuvanted formulations [6]
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