Immunoprotection of Mice against Schistosomiasis Mansoni Using Solubilized Membrane Antigens

Abstract

BackgroundSchistosomiasis continues to be one of the most prevalent parasitic diseases in the world. Despite the existence of a highly effective antischistosome drug, the disease is spreading into new areas, and national control programs do not arrive to complete their tasks particularly in low endemic areas. The availability of a vaccine could represent an additional component to chemotherapy. Experimental vaccination studies are however necessary to identify parasite molecules that would serve as vaccine candidates. In the present work, C57BL/6 female mice were subcutaneously immunized with an n-butanol extract of the adult worm particulate membranous fraction (AWBE) and its protective effect against a S. mansoni challenge infection was evaluated.Methodology and FindingsWater-saturated n-butanol release into the aqueous phase a set of membrane-associated (glyco)proteins that are variably recognized by antibodies in schistosome-infected patients; among the previously identified AWBE antigens there is Alkaline Phosphatase (SmAP) which has been associated with resistance to the infection in mice. As compared to control, a significantly lower number of perfuse parasites was obtained in the immunized/challenged mouse group (P<0.05, t test); and consequently, a lower number of eggs and granulomas (with reduced sizes), overall decreasing pathology. Immunized mice produced high levels of sera anti-AWBE IgG recognizing antigens of ∼190-, 130-, 98-, 47-, 28-23, 14-, and 9-kDa. The ∼130-kDa band (the AP dimer) exhibited in situ SmAP activity after addition of AP substrate and the activity was not apparently inhibited by host antibodies. A preliminary proteomic analysis of the 25-, 27-, and 28-kDa bands in the immunodominant 28–23 kDa region suggested that they are composed of actin.ConclusionsImmunization with AWBE induced the production of specific antibodies to various adult worm membrane molecules (including AP) and a partial (43%) protection against a challenging S. mansoni infection by mechanism(s) that still has to be elucidated.

Immunogenicity Assessment for Lung-Stage and Biomphalaria Alexandrina Cocktail Vaccine in Schistosoma Mansoni Infected Mice

“…cidence and prevalence into new countries (Sulbara et al, 2013). Basyoni and Abd El-Wahab ( 2013) reported that B. alexandrina antigen was good one among other antigens that can replace adult S. mansoni crude antigen in diagnosis and thus for vaccination.…”

An invertebrate smooth muscle with striated muscle myosin filaments

“…S. mansoni adult worms ["JL strain, Venezuela," maintained at the Instituto Venezolano de Investigaciones Científicas (IVIC) Trematodiasis Unit] were obtained by perfusion from the portal vein of golden hamsters infected with 500 cercariae (16). All procedures involving animals were performed according to the National Guidelines for Laboratory Animals established by the "Asociación Venezolana de Bioterios."…”

“…Our interest in these muscles was catalyzed by reports that the drug used to treat schistosomiasis (praziquantel) may act on the myosin molecule (15), and that muscle proteins like myosin, paramyosin, and certain regions of actin might be useful targets for the development of an antischistosomal vaccine or chemotherapy (16)(17)(18). We show that the adult form of S. mansoni has exclusively smooth muscles, and yet its thick filaments have the bipolar, helical structure characteristic…”

Immunization with adultSchistosoma mansonitegument, treated with sub-curative praziquantel, partially protects mice against the infection

“…Treatment of adult schistosome worm tegument with sub-curative PZQ enhanced its protective effects: in vitro TT induced the highest protection value by 51.8–57%, and in vivo TT caused 44.6–50.2% reductions in the adult worm burden when compared to the PBS + adjuvant. This level of protection was comparable to tegumental preparations so far used in murine schistosomiasis vaccine, such as tegumental glycosyl phosphatidyl inisotol (GPI)-anchored proteins that induced 42% reduction of the adult worm burden (Martins et al , 2012), use of an n-butanol extract of adult S. mansoni worm membrane fraction that resulted in 40.7–62.4% fewer adult worms than in control mice (Sulbaran et al ., 2013), and fused Sm14/29 formulated with polyinosinic-polycytidylic acid adjuvant (polyI:C) that induced 48.4% protection (Mossallam et al , 2015). Furthermore, in vitro TT induced the highest reduction in tissue egg numbers, followed by in vivo TT.…”