Recombinant proteins of helminths with immunoregulatory properties and their possible therapeutic use

Santos, Leonardo Nascimento; Pacheco, Luis Gustavo Carvalho; Pinheiro, Carina S.; Alcantara-Neves, Neuza Maria

doi:10.1016/j.actatropica.2016.11.016

Cited by 20 publications

(9 citation statements)

References 110 publications

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“…It has also been indicated that tick-derived carbohydrates (such as alpha fucosylation of tick glycoproteins by fucosyltransferases) are role-players in tick-pathogen interactions, such as colonization and transmission in vector cells (e.g., Anaplasma phagocytophilum ) (de La Fuente et al, 2006 ; Pedra et al, 2010 ; Cabezas-Cruz et al, 2017 ). Similar studies in schistosomes have indicated an important role of glycan epitopes in host-parasite interactions including modulation and evasion of host innate and adaptive immunity, as well as infection biology during snail-schistosome interactions (e.g., fucosylated structures produced on larval surfaces and released during larval transformation and sporocyst development) (Mickum et al, 2014 ; Jurberg and Brindley, 2015 ; Smit et al, 2015 ; Nascimento Santos et al, 2017 ). Investigation of carbohydrate-protein interactions have been revolutionized with the development of functional glycomics tools such as glycan arrays that have been applied successfully in the analysis of glycan binding protein associated biology, host-pathogen interactions and immune recognition (by antigen specific antibodies) (Heimburg-Molinaro et al, 2011 ; Rillahan and Paulson, 2011 ; Arthur et al, 2014 ).…”

Section: Metazoan Vaccine Development: Identification To Formulationmentioning

confidence: 83%

Metazoan Parasite Vaccines: Present Status and Future Prospects

Stutzer

Richards

Ferreira

et al. 2018

Front. Cell. Infect. Microbiol.

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Eukaryotic parasites and pathogens continue to cause some of the most detrimental and difficult to treat diseases (or disease states) in both humans and animals, while also continuously expanding into non-endemic countries. Combined with the ever growing number of reports on drug-resistance and the lack of effective treatment programs for many metazoan diseases, the impact that these organisms will have on quality of life remain a global challenge. Vaccination as an effective prophylactic treatment has been demonstrated for well over 200 years for bacterial and viral diseases. From the earliest variolation procedures to the cutting edge technologies employed today, many protective preparations have been successfully developed for use in both medical and veterinary applications. In spite of the successes of these applications in the discovery of subunit vaccines against prokaryotic pathogens, not many targets have been successfully developed into vaccines directed against metazoan parasites. With the current increase in -omics technologies and metadata for eukaryotic parasites, target discovery for vaccine development can be expedited. However, a good understanding of the host/vector/pathogen interface is needed to understand the underlying biological, biochemical and immunological components that will confer a protective response in the host animal. Therefore, systems biology is rapidly coming of age in the pursuit of effective parasite vaccines. Despite the difficulties, a number of approaches have been developed and applied to parasitic helminths and arthropods. This review will focus on key aspects of vaccine development that require attention in the battle against these metazoan parasites, as well as successes in the field of vaccine development for helminthiases and ectoparasites. Lastly, we propose future direction of applying successes in pursuit of next generation vaccines.

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Section: Metazoan Vaccine Development: Identification To Formulationmentioning

confidence: 83%

Metazoan Parasite Vaccines: Present Status and Future Prospects

Stutzer

Richards

Ferreira

et al. 2018

Front. Cell. Infect. Microbiol.

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“…It is likely that many mechanisms are contributing simultaneously to immunomodulation. The proteins previously reported ( 24 , 27 , 28 , 37 ) may have a primary or secondary role in immune regulation. The cystatins, which have been reported to play an immunomodulatory role in several parasites ( 121 – 123 ), would likely inhibit cathepsin function and, hence, peptide excision for presentation on the MHC.…”

Section: Discussionmentioning

confidence: 93%

“…A set of sequences for proteins previously reported to be associated with immunomodulation ( 24 , 28 , 37 ) was assembled, using Reference sequences from GenBank. These proteins are listed in Table S1 in Supplementary Material.…”

Section: Methodsmentioning

confidence: 99%

“…Treatment with anthelminthics removes this effect and is reported to increase the incidence of inflammatory, autoimmune and allergic diseases ( 22 , 23 ). The observation that helminth infection modulates inflammation and allergic responses has raised interest in the use of helminth infections, helminth extracts, or recombinant helminth-derived proteins as therapeutic interventions ( 24 – 27 ).…”

Section: Introductionmentioning

confidence: 99%

“…Extracts of secreted and surface proteins have been shown experimentally to elicit some of the immunomodulatory effects ( 32 , 34 ). This has been extended to testing a number of individual proteins and identifying several proteins that can affect immune function ( 24 , 28 , 31 , 37 ). The second unifying theme is that T regulatory (Treg) cells, and induction of IL-10, play a central role in helminth-induced host immune modulation ( 38 – 44 ), whether by classical Foxp3+ CD4 cells or other IL-10 secreting populations of CD4+ or CD8+ cells ( 45 – 50 ).…”

Section: Introductionmentioning

confidence: 99%

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A Role for Epitope Networking in Immunomodulation by Helminths

Homan¹,

Bremel²

2018

Front. Immunol.

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Helminth infections, by nematodes, trematodes, or cestodes, can lead to the modulation of host immune responses. This allows long-duration parasite infections and also impacts responses to co-infections. Surface, secreted, excreted, and shed proteins are thought to play a major role in modulation. A commonly reported feature of such immune modulation is the role of T regulatory (Treg) cells and IL-10. Efforts to identify helminth proteins, which cause immunomodulation, have identified candidates but not provided clarity as to a uniform mechanism driving modulation. In this study, we applied a bioinformatics systems approach, allowing us to analyze predicted T-cell epitopes of 17 helminth species and the responses to their surface proteins. In addition to major histocompatibility complex (MHC) binding, we analyzed amino acid motifs that would be recognized by T-cell receptors [T-cell-exposed motifs (TCEMs)]. All the helminth species examined have, within their surface proteins, peptides, which combine very common TCEMs with predicted high affinity binding to many human MHC alleles. This combination of features would result in large cognate T cell and a high probability of eliciting Treg responses. The TCEMs, which determine recognition by responding T-cell clones, are shared to a high degree between helminth species and with Plasmodium falciparum and Mycobacterium tuberculosis, both common co-infecting organisms. The implication of our observations is not only that Treg cells play a significant role in helminth-induced immune modulation but also that the epitope specificities of Treg responses are shared across species and genera of helminth. Hence, the immune response to a given helminth cannot be considered in isolation but rather forms part of an epitope ecosystem, or microenvironment, in which potentially immunosuppressive peptides in the helminth network via their common T-cell receptor recognition signals with T-cell epitopes in self proteins, microbiome, other helminths, and taxonomically unrelated pathogens. Such a systems approach provides a high-level view of the antigen-immune system signaling dynamics that may bias a host’s immune response to helminth infections toward immune modulation. It may indicate how helminths have evolved to select for peptides that favor long-term parasite host coexistence.

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