Secreted and membrane-bound (S/M) protein of some important helminths of man.
Abstract
Hydatidosis or cystic echinococcosis (CE) is caused by the larval stage of the tapeworm Echinococcus granulosus. This parasite is cosmopolitan in distribution and causes significant economic losses to the meat industry, mainly due to condemnation of edible offal. Echinococcosis treatment in human is very expensive as it requires extensive surgery or prolonged chemotherapy or use of both. In Asia and Africa, the vulnerable population of developing the disease is around 50 million. Office International des Epizooties (OIE) has recognized CE as a multi species disease. The parasite has acquired the capability to survive long time within the host due to a specific mechanism to evade the host immune system. A specific class of proteins known as secreted and membrane bound (S/M) proteins play key roles in the evasion mechanism. A total of 12 S/M proteins have been reported as immunodiagnostic and immunoprophylactic agents. Of these, Eg95 is a candidate antigen used for immunization of animals. Literature suggests that, Eg95 is a multi-gene family (Eg95-1 to Eg95-7) and exists in seven different isoforms. This chapter will describe minutely efficacy of Eg95 as a vaccine candidate based on animal trial and potentiality of other S/M proteins as immunodiagnostic antigen and immune evasion.
Keywords
- Echinococcus granulosus
- cystic echinococcosis
- secreted and membrane-bound (S/M) proteins
- vaccine
1. Introduction
2. Secreted and membrane-bound (S/M) proteins for sustenance within host: a weapon of parasite against host environment
We felt it judicious that, before we discuss about an Eg95 vaccine and secreted and membrane-bound (S/M) proteins of
S. No. | Name of the parasite | Name of S/M protein | Activity |
---|---|---|---|
1. | Chemokine binding Protein | Neutralization of chemokine activity (CXCL8, CCL3, CX3CL1, CCL2, CCL5); inhibits neutrophil migration [5] et al. | |
2. | Helminth defense molecule-1 | Molecular mimicry of antimicrobial peptides, binds to LPS and reduces its activity; prevents acidification of the endolysosomal compartments and antigen processing; prevents NLRP3 inflammasome activation [6, 7]. | |
Fatty acid binding protein | Suppresses LPS-induced activation via binding and blocking of CD14; induction of alternatively activated macrophages [8] | ||
TGF-like molecule | Ligates mammalian TGF-b receptor (albeit with a lower affinity) and induces IL-10 and Arginase in macrophages [9] | ||
3. | Asparaginyl-tRNA synthetase | Structural homology to IL-8, binds IL-8 receptors CXCR1 and CXCR2; chemotactic for neutrophils and eosinophils; induced regulatory responses and IL-10 in a T cell transfer model of colitis [10] | |
TGF-b homolog-2 | Ligates mammalian TGF-b receptor and suppresses T cell responses [11] | ||
Abundant larval transcript | Inhibitor of IFN-¥ signaling [11] | ||
4. | Metalloproteinases | Causes proteolysis of eotaxin, but not of IL-8 or eotaxin-2 [12] | |
Binding to CD79A on B cells, downregulation of lyn,PI3K, and BCR signaling [13] | |||
5. | Acetylcholinesterase | Degrades acetylcholine, reduces neural signaling; induces proinflammatory cytokines with diminished type 2 cytokines in transgenic AChE-expressing trypanosome infection [14] | |
6. | T cell immunomodulatory protein | Induces release of IFN-g from CD4+ T cells in vitro [15] |
3. Introducing S/M proteins of E. granulosus
This is better to understand about S/M proteins of
3.1 Antigen B
Antigen B (AgB) is an oligomeric thermostable lipoprotein. The antigen was first described by Oriolet al. [16]. The protein was separated from the hydatid fluid by size-exclusion chromatography as a 160 kDa protein. This protein is abundantly present in
3.2 Antigen 5
Antigen 5 (Ag5) is a major antigen of
3.3 14-3-3 Protein
14-3-3 proteins are a group of molecules that are of different isoforms. These molecules are distributed in a broad range of cells in all eukaryotic organisms. These groups of molecules are highly conserved in nature and were first reported from brain tissue. In recent time, they were found to play crucial roles in eukaryotic cell cycling. 14-3-3 Proteins bind with specific ligands containing phosphorylated serine/threonine residues to form homo- and heterodimer complexes, and this process is regulated by phosphorylation. Several mechanisms of action of 14-3-3 proteins have been reported; such as induction of conformational change of target molecules, the physical occluding of specific features, the scaffolding, and the change of cellular localization. The 14-3-3 proteins are acidic protein with a relative molecular weight of 30 kDa. This group of proteins show 50% identity within and across species, small (30 kDa), acidic proteins that show about 50% amino acid identity both within and across species. In mammals, seven isoforms have been identified (b-beta, c-gamma, f-zeta, r-sigma, e-epsilon, g-eta, and s-tau). The 14-3-3f isoforms also termed as
4. Eg95: a brief introduction
Concept to develop Eg95 (16.6 kDa protein) was initiated on the basis of identification of individual oncosphere components that stimulate host-protective immune responses in sheep. Marathon effort was made on this aspect by Heath and Lawrence [29] on identification and characterization of host protective antigen hither-to its testing in vaccine trial. For raising the hyperimmune sera, the group of workers used whole
4.1 Isoforms of Eg95 antigen
A protein isoform is known as protein variant. They rise from a single gene or a gene family. Protein isoforms are formed due to alternative splicings or variable use of promoter or sometimes may be due to post-transcriptional modification of a single gene [30, 31]. Agene family of Eg95 for common sheep strain (G1) of
Based on phylogenetic analysis (Figure 1), this was evidenced that Eg95 gene family is having two clusters (Eg95 1-4 and Eg 95 5-6). From India, an elaborative study was done to know the genetic diversity of Eg95 [33]. A total of 24 isolates collected from cattle, buffalo, sheep, goat, human, and dog were analyzed. Genotypic characterization of these isolates revealed that all isolates belonged to G1 genotype except one buffalo isolate, which was characterized as cattle strain (G5). Phylogenetically, the Eg95 coding gene characterized from Indian isolates of
4.2 Eg95 as vaccine
As a vaccine Eg95 is very effective to control
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