Advances in the Study of Schistosomiasis: The Postgenomic Era (original) (raw)
Related papers
Schistosoma Tegument Proteins in Vaccine and Diagnosis Development: An Update
Journal of Parasitology Research, 2012
The development of a vaccine against schistosomiasis and also the availability of a more sensitive diagnosis test are important tools to help chemotherapy in controlling disease transmission. Bioinformatics tools, together with the access to parasite genome, published recently, should help generate new knowledge on parasite biology and search for new vaccines or therapeutic targets and antigens to be used in the disease diagnosis. Parasite surface proteins, especially those expressed in schistosomula tegument, represent interesting targets to be used in vaccine formulations and in the diagnosis of early infections, since the tegument represents the interface between host and parasite and its molecules are responsible for essential functions to parasite survival. In this paper we will present the advances in the development of vaccines and diagnosis tests achieved with the use of the information from schistosome genome focused on parasite tegument as a source for antigens.
Investigación clínica, 2011
Understanding the mode of Schistosoma mansoni larval invasion and the mechanism of immune evasion utilized by larvae and adult worms is essential for a rational development of vaccines or drugs to prevent or cure the disease. This parasite has a very complex molecular organization in all parasite stages, and identifying the major parasite proteins would give clues to schistosome metabolism and to the interaction of the parasite with the host immune system. Our goal was the evaluation of the protein parasite repertoire using a proteomic approach, and the characterization of protein extracts from two different parasite stages of a Venezuelan isolate, such as cercariae and adult worms, previously performed by other authors in some other strains. A comparison among authors was made. Besides, we aimed to identify different isoforms of one of the vaccine candidates, the gluthation-S-transferase protein (Sm28GST), by 2D SDS-PAGE and mass spectrometry, and to achieve its immunologic detecti...
Frontiers in immunology, 2015
Schistosomiasis is a debilitating disease that represents a major health problem in at least 74 tropical and subtropical countries. Current disease control strategies consist mainly of chemotherapy, which cannot prevent recurrent re-infection of people living in endemic area. In the last decades, many researchers made a remarkable effort in the search for an effective vaccine to provide long-term protection. Parasitic platyhelminthes of Schistosoma genus, which cause the disease, live in the blood vessels of definitive hosts where they are bathed in host blood for many years. Among the most promising molecules as vaccine candidates are the proteins present in the host-parasite interface, so numerous tegument antigens have been assessed and the achieved protection never got even close to 100%. Besides the tegument, the digestive tract is the other major site of host-parasite interface. Since parasites feed on blood, they need to swallow a considerable amount of blood for nutrient acq...
Schistosomiasis vaccine discovery using immunomics
Parasites & Vectors, 2010
The recent publication of the Schistosoma japonicum and S. mansoni genomes has expanded greatly the opportunities for post-genomic schistosomiasis vaccine research. Immunomics protein microarrays provide an excellent application of this new schistosome sequence information, having been utilised successfully for vaccine antigen discovery with a range of bacterial and viral pathogens, and malaria. Accordingly, we have designed and manufactured a Schistosoma immunomics protein microarray as a vaccine discovery tool. The microarray protein selection combined previously published data and in silico screening of available sequences for potential immunogens based on protein location, homology to known protective antigens, and high specificity to schistosome species. Following cloning, selected sequences were expressed cell-free and contact-printed onto nitrocellulose microarrays. The reactivity of microarray proteins with antisera from schistosomiasisexposed/resistant animals or human patients can be measured with labelled secondary antibodies and a laser microarray scanner; highly reactive proteins can be further assessed as putative vaccines. This highly innovative technology has the potential to transform vaccine research for schistosomiasis and other parasitic diseases of humans and animals.
Editorial: The Schistosomiasis Vaccine – It is Time to Stand up
Frontiers in Immunology, 2015
Schistosomiasis is a severe parasitic disease, endemic in 74 developing countries with up to 600 million people infected and 800 million, mostly children, at risk of contracting the disease following infection predominantly with Schistosoma mansoni, Schistosoma haematobium, or Schistosoma japonicum. The disease burden is estimated to exceed 70 million disability-adjusted life-years, and leads to remarkably high YLD (years lived with disability) rates. Even more importantly, people with schistosomiasis are highly susceptible to malaria, tuberculosis, and hepatic and acquired immunodeficiency viruses. There is only one drug, praziquantel, currently available for treatment and it has high efficacy, low cost, and limited side effects. However, only 13% of the target population has received the drug, and those treated are at continuous risk of reinfection necessitating repeated drug administration and the emergence of drug-resistant parasites is a constant threat (1). Currently there is no vaccine. The a priori requirements for discovery of a vaccine formulation include the following: identification of protective key immune players in humans; characterization and isolation of target antigens; establishment of efficacy in terms of reduction of parasite burden as well as amelioration of immunopathology; establishment of safety; and finally, provision of considerable funds along with physical infrastructure and qualified personnel to carry out clinical trials. The target of >40% protection has been achieved with some schistosome molecules such as fatty acid binding protein (Sm14), paramyosin, calpain large subunit (Sm80), superoxide dismutase (SOD), glutathione S-transferase (GST), glyceraldehyde 3-phosphate dehydrogenase, and cysteine peptidases (2). Furthermore, Pearson et al. (3) identified the antigens selectively recognized by serum IgG1 and IgE of S. haematobium patients who acquired praziquantel-induced resistance (DIR) to the infection, or self-cured macaques following S. japonicum infection. The probed antigens were derived from S. mansoni and S. japonicum, likely because of the documented antigen conservation among the three main clinically important species, and were selected among those known to be secreted or localized to the tegument. The tegument is at the host-parasite interface, but its access by host effector antibodies is entirely prevented in healthy schistosomes, otherwise they would not survive a day, not to mention decades, in the host bloodstream. Anyhow, the study identified once again calpain, SOD, and GST as vaccine candidates together with surface membrane-associated antigens such as tetraspanins and glucose transporters, as well as an array of newly discovered target antigens. A remarkable finding in the study was the implication that type 2 (IgG1 and IgE) and not type 1-related antibodies are critical for human resistance against S. haematobium reinfection. Besides the worm tegument, which may not be accessed by host effector antibodies, the digestive tract is the other major interface between host and parasite. Schistosome peptidases responsible for digesting blood-born cells, components, and nutrients may be targeted, and possibly neutralized and blocked, by host antibodies and, thus, represent potential vaccine candidates. The timely study of Figueiredo et al. (4) reviewed what is known about the properties and vaccine potential of proteins secreted by the esophagus, and the lining (gastrodermis) of the blind-ended gut, namely Sm14, Sm10.3, venom allergen-like (VAL) protein, Cu-Zn SOD, cathepsin B, and cathepsin L.
The Schistosoma japonicum genome reveals features of host–parasite interplay
Nature, 2009
Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signalling pathways for growth, development and maturation. Having a complex nervous system and a well-developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control.
Trends in Parasitology, 2011
Schistosoma genomes provide a comprehensive resource for identifying the molecular processes that shape parasite evolution and for discovering novel chemotherapeutic or immunoprophylactic targets. Here, we demonstrate how intra-and intergenus comparative genomics can be used to drive these investigations forward, illustrate the advantages and limitations of these approaches and review how post genomic technologies offer complementary strategies for genome characterisation. While sequencing and functional characterisation of other schistosome/ platyhelminth genomes continues to expedite anthelmintic discovery, we contend that future priorities should equally focus on improving assembly quality, and chromosomal assignment, of existing schistosome/platyhelminth genomes. Comparative genome basics July 2009 marked a seminal date in the history of parasite genomics, helminthology and evolutionary biology. After more than 20 years of collaborative research, both Schistosoma japonicum[1] and Schistosoma mansoni[2] draft genomes were elucidated using wholegenome shotgun sequencing (Glossary). Along with Schistosoma haematobium, these parasitic trematodes are responsible for most cases of human hepatosplenic (S. japonicum and S. mansoni) and urinary (S. haematobium) schistosomiasis[3], a chronic and morbid neglected tropical disease afflicting hundreds of millions of people in sub-Saharan Africa, Asia and South America[4]. Information contained in these genomes has fuelled optimism
Clinical and Experimental Immunology, 2006
Surface proteins of schistosomes are exposed to host tissues and thus present as potential candidate molecules for the development of new intervention strategies. Herein, we have identified a new tegumental protein of Schistosoma mansoni , termed Sm29. In silico analysis revealed a signal peptide, three glycosylation sites and a transmembrane region on Sm29 amino acid sequence. Sm29 transcription in mammalian developmental stages cDNA libraries of S. mansoni was verified by PCR using specific primers for Sm29 nucleotide sequence and it revealed the presence of transcripts in schistosomula and adult worm stages of the parasite. Sm29 (40-169) fragment was produced in Escherichia coli and purified by affinity chromatography to be used in the immunological assays. Confocal microscopy confirmed bioinformatic studies, revealing that Sm29 is a membranebound protein localized on the tegument of S. mansoni adult worm. ELISA was performed using rSm29 protein to investigate the antibody isotype profile to Sm29 in sera of patients living in endemic areas for schistosomiasis. IgG1 and IgG3 subclass antibodies to rSm29 were predominant in sera of individuals naturally resistant to infection and resistant to re-infection whereas low levels of IgM, IgA or IgE were measured. Since, IgG1 and IgG3 are involved in parasite killing and in protective immunity the findings reported here suggest the use of Sm29 as a potential candidate vaccine against schistosomiasis.
PLOS Neglected Tropical Diseases, 2008
Background: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membranespanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate.