Schistosoma mansoni lung-stage larvae are known to be the major target of innate and acquired immunity to schistosomiasis. Lung schistosomula cytosolic or surface membrane antigens are hidden, entirely inaccessible to the host immune system, and hence are not particularly important as vaccine candidates. Conversely, excretory-secretory (E-S) products released from intact, viable, elongated, and contractile schistosomula are ideal potential vaccines, as such molecules can readily play a central role in the induction of local primary and memory immune response effectors that would directly target, surround, and pursue the larvae while negotiating the lung capillaries. Therefore, 6-day-old ex vivo larvae were isolated from mouse or hamster lung cells and used for generation of E-S products, which were shown to elicit strong immune responses and significant (P<0.05) protection against challenge infection in BALB/c mice. Proteomic analysis of E-S molecules following 10x concentration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis identified peptides related to innumerable host and about 15 S. mansoni-specific proteins. Selected S. mansoni-specific E-S peptides prepared in a multiple antigen peptide (MAP) or recombinant form were shown to stimulate considerable specific antibody response and peripheral blood mononuclear cell expression of mRNA for several cytokines in immunized C57BL/6 and BALB/c mice. However, highly significant (P<0.05 to <0.005) reduction in challenge infection worm burden and egg load was recorded only when the immunization conditions in test mice provided the S. mansoni antigen-specific T helper (Th) type response milieu favorable for each immunogen. That was polarized Th1 for S. mansoni aldolase and thioredoxin peroxidase 1 MAPs, polarized Th2 for recombinant 14-3-3-like protein, mixed Th1/Th17 for calpain MAP, and mixed Th1/Th2 for recombinant p18 protein. The findings together indicated that the immune responses issue is as critical as the nature and source of the antigen for the development of vaccine against schistosomiasis.
"This time point was selected as it corresponds to the approximate time when invading larvae reach the lung, documented as the major site of parasite attrition (Dean and Mangold, 1992; Coulson, 1997). 2 A.M. Badr et al. Lung larval excretory–secretory antigens (ESP) Purified recombinant lung-stage ESP vaccine antigens included S. mansoni 14-3-3 like-protein and P18 (El Ridi and Tallima, 2009). cDNA clone encoding P18 antigen was expressed using Champion pET SUMO Protein Expression Kit. "
[Show abstract][Hide abstract] ABSTRACT: In contrast to mice, rats are less-susceptible to infection with Schistosoma mansoni, perhaps mounting protective immune responses that provide a microenvironment unfavorable for the normal growth and survival of the parasite. Upon infection, schistosomular excretory–secretory products (ESP) trigger T helper (Th) effector cells and polarize the immune microenvironment. We investigated the differences in mouse and rat immune responses to the larval ESP, 14-3-3-like protein, P18, and fructose-1,6-bisphosphate aldolase, prepared in a recombinant or multiple antigen peptide form. Ex vivo spleen cells (SC) of naïve, and 7 day-S. mansoni-infected CD1 mice and Wistar rats were stimulated in vitro with the selected ESP, and the culture supernatants were assessed for cytokine levels by capture enzyme-linked immunosorbent assay. S. mansoni ESP failed to induce SC of 7 day-infected mice to produce detectable interleukin (IL)-4 levels, but led to significant increase in released interferon-gamma (IFN-γ) as compared to naïve mice. Conversely, SC of rats released significant IL-4 levels in response to ESP stimulation, while IFN-γ was hardly detected in the supernatants. Amounts of ESP-specific antibodies in infected rats were significantly higher than in infected mice. Our results suggest that resistance to schistosomiasis is associated with type 2 cytokines and high levels of parasite ESP-specific antibodies.
"Therefore, the ESP represents a potential pool of vaccine targets. A number of ESP of cercariae, in vitro-cultured and ex vivo lung-stage schistosomula, and adult worms of S. mansoni (Harrop et al., 1999; Knudsen et al., 2005; Curwen et al., 2006; Hansell et al., 2008; El Ridi and Tallima, 2009), S. japonicum (Liu et al., 2009; Liao et al., 2011) and S. haematobium (Young et al., 2012) have been identified; molecules common to these preparations include actin, heat shock proteins, enolase, aldolase, glutathione S-transferase, triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH), 2 cis-peroxyredoxin (PRX), and serine and, predominantly, cysteine peptidases. "
[Show abstract][Hide abstract] ABSTRACT: Each year schistosomiasis afflicts up to 600 million people in 74 tropical and sub-tropical countries, predominantly in the developing world. Yet we depend on a single drug, praziquantel, for its treatment and control. There is no vaccine available but one is urgently needed especially since praziquantel-resistant parasites are likely to emerge at some time in the future. The disease is caused by several worm species of the genus Schistosoma. These express several classes of papain-like cysteine peptidases, cathepsins B and L, in various tissues but particularly in their gastrodermis where they employ them as digestive enzymes. We have shown that sub-cutaneous injection of recombinant and functionally active Schistosoma mansoni cathepsin B1 (SmCB1), or a cathepsin L from a related parasite Fasciola hepatica (FhCL1), elicits highly significant protection (up to 73%) against an experimental challenge worm infection in murine models of schistosomiasis. The immune modulating properties of this subcutaneous injection can boost protection levels (up to 83%) when combined with other S. mansoni vaccine candidates, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) and peroxiredoxin (PRX-MAP). Here, we discuss these data in the context of the parasite's biology and development, and provide putative mechanism by which the native-like cysteine peptidase induce protective immune responses.
Frontiers in Genetics 05/2014; 5:119. DOI:10.3389/fgene.2014.00119
"The calcium-dependent, neutral cysteine-protease (calpain) was previously purified from S. mansoni  and reported to be excreted/secreted  and present on the tegument surface . The large subunit of calpain (Sm-p80) was tested as recombinant vaccine which provided a 29–39% reduction in worm burden in immunized mice challenged with S. mansoni . "
[Show abstract][Hide abstract] ABSTRACT: The flatworm Schistosoma mansoni is a blood fluke parasite that causes schistosomiasis, a debilitating disease that occurs throughout the developing world. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control schistosomiasis is through immunization with an antischistosomiasis vaccine combined with drug treatment. Several papers on Schistosoma mansoni vaccine and drug development have been published in the past few years, representing an important field of study. The advent of technologies that allow large-scale studies of genes and proteins had a remarkable impact on the screening of new and potential vaccine candidates in schistosomiasis. In this postgenomic scenario, bioinformatic technologies have emerged as important tools to mine transcriptomic, genomic, and proteomic databases. These new perspectives are leading to a new round of rational vaccine development. Herein, we discuss different strategies to identify potential S. mansoni vaccine candidates using computational vaccinology.
BioMed Research International 10/2011; 2011(5):503068. DOI:10.1155/2011/503068 · 2.71 Impact Factor
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