Faculty Opinions recommendation of Nucleic acid vaccination with Schistosoma mansoni antioxidant enzyme cytosolic superoxide dismutase and the structural protein filamin confers protection against the adult worm stage.

ABSTRACT Schistosomiasis remains a worldwide endemic cause of chronic and debilitating illness. There are two paradigms that exist in schistosome immunology. The first is that the schistosomule stages are the most susceptible to immune killing, and the second is that the adult stage, through evolution of defense mechanisms, can survive in the hostile host environment. One mechanism that seems to aid the adult worm in evading immune killing is the expression of antioxidant enzymes to neutralize the effects of reactive oxygen and nitrogen species. Here, we challenge one paradigm by targeting adult Schistosoma mansoni worms for immune elimination in an experimental mouse model using two S. mansoni antioxidants, cytosolic superoxide dismutase (SmCT-SOD) and glutathione peroxidase (SmGPX), and a partial coding sequence for a structural protein, filamin, as DNA vaccine candidates. DNA vaccination with SmCT-SOD induced a mean of 39% protection, filamin induced a mean of 50% protection, and SmGPX induced no protection compared to controls following challenge with adult worms by surgical transfer. B- and T-cell responses were analyzed in an attempt to define the protective immune mechanism(s) involved in adult worm killing. SmCT-SOD-immunized mice presented with a T1 response, and filamin-immunized mice showed a mixed T1-T2 response. We provide evidence for natural boosting after vaccination. Our results demonstrate that adult worms can be targeted for immune elimination through vaccination. This represents an advance in schistosome vaccinology and allows for the development of a therapeutic as well as a prophylactic vaccine.

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Immunoprecipitins in human schistosomiasis detected with adult worm antigens released by 3M KC1

Journal of Helminthology ◽

10.1017/s0022149x00007276 ◽

1977 ◽

Vol 51 (1) ◽

pp. 71-72 ◽

Cited By ~ 3

Author(s):

Mauro Scapin ◽

Miriam Tendler

Keyword(s):

Schistosoma Mansoni ◽

Adult Worm ◽

Calcium Chloride ◽

Surface Proteins ◽

Immunochemical Characterization ◽

Human Schistosomiasis

Several methods are being applied for solubilizing adult Schistosoma mansoni antigens which may allow their immunochemical characterization and purification. Studies on antigens and immunoprecipitins in schistosome infections have been carried out with homogenized extracts of adult worms and/or larval forms of Schistosoma mansoni in saline (Biguet et al., 1962; Kagan and Norman, 1963; Silva and Ferri, 1965), or water (Kent, 1963). Kusel (1972) studied surface proteins in S. mansoni membrane, treating the worms with 0·5% saponin in 3% calcium chloride. Murrel et al. (1974) compared by immunodiffusion a crude culture antigen with extracts obtained by freeze-thawing of adult worms and by treatment in 3M KCl.

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Attempts to Induce Resistance against Schistosoma mansoni by Injecting Cercarial, Adult Worm, and Egg Homogenates in Sequence

Journal of Parasitology ◽

10.2307/3275571 ◽

1962 ◽

Vol 48 (2) ◽

pp. 233 ◽

Cited By ~ 11

Author(s):

Lawrence S. Ritchie ◽

Seymour Garson ◽

Duane G. Erickson

Keyword(s):

Schistosoma Mansoni ◽

Adult Worm ◽

Induce Resistance

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Oxygen tolerance and occurrence of superoxide dismutase as an antioxidant enzyme in Metopus es

Research in Microbiology ◽

10.1016/j.resmic.2010.01.009 ◽

2010 ◽

Vol 161 (3) ◽

pp. 227-233 ◽

Cited By ~ 1

Author(s):

Nimi Narayanan ◽

Bhaskaran Krishnakumar ◽

Vattakkatt Balakrishnan Manilal

Keyword(s):

Superoxide Dismutase ◽

Antioxidant Enzyme ◽

Oxygen Tolerance

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In vitro effects of artesunate on the survival of worm pairs and egg production of Schistosoma mansoni

Journal of Helminthology ◽

10.1017/s0022149x08070235 ◽

2009 ◽

Vol 83 (1) ◽

pp. 7-11 ◽

Cited By ~ 23

Author(s):

Y. Mitsui ◽

M. Miura ◽

Y. Aoki

Keyword(s):

Schistosoma Mansoni ◽

Adult Worm ◽

Survival Time ◽

Egg Production ◽

Inhibitory Effect ◽

Male And Female ◽

Paired Male ◽

In Vitro Effects ◽

Paired Female

AbstractThe effect of artesunate (ART) on the survival time of adult worm pairs of Schistosoma mansoni and on their egg output during in vitro culture was assessed. ART significantly decreased the survival time of both paired male and female worms at concentrations of 5, 10, 20 and 40 mg l− 1 during in vitro cultivation. An inhibitory effect of ART on the daily egg output of paired female worms during in vitro cultivation was also observed.

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Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.2.1003 ◽

1989 ◽

Vol 66 (2) ◽

pp. 1003-1007 ◽

Cited By ~ 35

Author(s):

C. W. White ◽

P. Ghezzi ◽

S. McMahon ◽

C. A. Dinarello ◽

J. E. Repine

Keyword(s):

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Antioxidant Enzyme ◽

Enzyme Activities ◽

Tumor Necrosis ◽

Interleukin 1 ◽

Antioxidant Enzyme Activities ◽

Rat Lung ◽

Glucose 6 Phosphate Dehydrogenase ◽

Necrosis Factor

Pretreatment with the combination of tumor necrosis factor/cachectin (TNF/C) and interleukin 1 (IL-1) increased glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD) activities in lungs of rats continuously exposed to hyperoxia for 72 h, a time when all untreated rats had already died. Pretreatment with TNF/C and IL-1 also increased, albeit slightly, lung G6PDH and GR activities of rats exposed to hyperoxia for 4 or 16 h. By comparison, no differences occurred in lung antioxidant enzyme activities of TNF/C and IL-1- or saline-pretreated rats exposed to hyperoxia for 36 or 52 h; the latter is a time just before untreated rats began to succumb during exposure to hyperoxia. The results raise the possibility that TNF/C and IL-1 treatment can increase lung antioxidant enzyme activities and that increased lung antioxidant enzymes may contribute to the increased survival of TNF/C and IL-1-pretreated rats in hyperoxia for greater than 72 h.

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