Schistosomes—proteomics studies for potential novel vaccines and drug targets

Abstract

Schistosomiasis is a major health problem and, despite decades of research, only one effective drug, Praziquantel is currently available. Recent expansion of sequence databases on Schistosoma mansoni and S. japonicum has permitted a wealth of novel proteomic studies on several aspects of the organization and development of the parasite in the human host. This unprecedented accumulation of molecular data is allowing a more rational approach to propose drug targets and vaccine candidates, such as proteins located at the parasite surface. Successful preliminary trials of two vaccine candidates that have been detected at the parasite surface by proteomics give grounds for believing that such an approach may provide a fresh start for the field.

Vaccinomics and a New Paradigm for the Development of Preventive Vaccines Against Viral Infections

“…Together they have been hailed as one of the 20th Century's most important public health achievements (Centers for Disease Control andPrevention, 1999a, 1999b). Nonetheless, barriers to the empirical approach have left many important infectious diseases (DeMarco and Verjovski-Almeida, 2009;Reed et al, 2006)-including a number of viral infections, such as respiratory syncytial virus (Murata, 2009;Varga, 2009), human immunodeficiency virus ( Johnston and Fauci, 2008), and herpes simplex (Mascola, 1999)-without safe and effective vaccines. These barriers include the following: Individuals do not appear to acquire long-lasting, effective immunity from an infection ( Johnston and Fauci, 2008;Mascola, 1999) Individuals require repeated infections to generate immunity (Reed et al 2006) The infectious agent rapidly mutates resulting in either numerous or sequentially different antigenic exposures (Murata, 2009;Rappuoli, 2007) Individuals can develop natural immunity from infection, but remain contagious ( Johnston and Fauci, 2008) Neutralizing antibodies alone do not effectively prevent infection (Rappuoli, 2007) Worse, antibodies formed build immune complexes causing harm (Varga, 2009) Individuals fail to respond immunologically to the infection, perhaps because of developmental immaturity of the immune system or because of interference from passively acquired maternal immunity (Murata, 2009) Nature lacks benign agents that result in mild infection but produce sufficient immunity The infectious agent cannot be attenuated without impairing the immunogenic qualities The attenuated form, although immunogenic, suffers from cold-chain issues preventing its distribution in parts of the world that cannot maintain a cold chain The attenuated form reverts to its more dangerous wild type The attenuated form still presents a danger despite attenuation to the immune compromised Where these barriers exist, we would propose a directed approach, moving away from the empirical approach that begins with the isolation of the immunizing agent followed by its modification.…”

Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

“…The landmark availability of the complete sequences of the S. japonicum (171) and S. mansoni (18) genomes will provide the necessary ancillary information. As well, new approaches in antigen discovery through the generation of a large schistosome transcriptome database, gene finding, and the explosion in postgenome technologies, including DNA microarray profiling, proteomics, glycomics, immunomics, and the application of RNA interference (RNAi) and novel imaging techniques (2,24,25,41,53,72,73,75,76,85,95,109,126,127,179,189,197,205,219,224,230), provide an unprecedented opportunity to identify a new generation of vaccine target molecules that may induce greater potency than the current candidate schistosome antigens (138).…”

It’s All about Those Bases: The Need for Incorporating Parasite Genetic Heterogeneity into the Development of Schistosome Vaccines

“…Moreover, apart from logistics and finances, development of appropriately robust references for each species required access to a single well-characterized lineage with ample biological resources. But now, with reference genomes [14–17], transcriptomes [15,18–20], exomes [21], phylogenomes [22], and proteomes [19,20,23] in hand, there exist a variety of resources that increase the ability of researchers to examine this variation. While not reflective of field variation, these resources vastly increase the ease of-omics work by providing a means for the creation of genetic tools [4] that can then be used in the field and a template that researchers can use to map their data.…”