Towards aTaenia soliumCysticercosis Vaccine: an Epitope Shared byTaenia crassicepsandTaenia soliumProtects Mice against Experimental Cysticercosis

Abstract

The Taenia crassiceps recombinant antigen KETc7 has been shown to be effective as a vaccine against experimental murine cysticercosis, a laboratory model used to test potentially promising molecules against porcine Taenia soliumcysticercosis. Based on the deduced amino acid sequence of this proline-rich polypeptide, three fragments, GK-1, GK-2, and GK-3, were chemically synthesized in linear form. Of the three peptides, only GK-1 induced sterile protection against T. crassicepscysticercosis in 40 to 70% of BALB/cAnN male mice. GK-1 is an 18-amino-acid peptide which contains at least one B-cell epitope, as demonstrated by its ability to induce an antibody response to the peptide and T. crassiceps antigen without need of a carrier protein. Immunofluorescence studies revealed that anti-GK1 antibodies strongly react with the native protein in the tegument ofT. crassiceps and also with anatomical structures ofT. solium eggs, oncospheres, cysticercus, and tapeworm. GK-1 also contains at least one T-cell epitope, capable of stimulating the proliferation of CD8+ and to a lower extent CD4+ T cells primed either with the free peptide orT. crassiceps total antigen. The supernatant of the stimulated cells contained high levels of gamma interferon and low levels of interleukin-4. Similar results were obtained with T cells tested for intracellular cytokine production, an indication of the peptide’s capacity to induce an inflammatory response. The remarkable protection induced by GK-1 immunization, its physicochemical properties, and its presence in all developmental stages ofT. solium point to this synthetic peptide as a strong candidate in the construction of a synthetic vaccine againstT. solium pig cysticercosis.

A self-aggregating peptide: implications for the development of thermostable vaccine candidates

“…Cell proliferation was evaluated using standard flow cytometry protocols [43,44]. After 5 days cells were harvested and stained with Phycoerythrin Cyanin 5.1 (PE-Cy™ 5)-conjugated anti-CD3 (BD Biosciences, USA, cat.…”

The Synthetic Parasite-Derived Peptide GK1 Increases Survival in a Preclinical Mouse Melanoma Model

“…In addition, GK1 is known to stimulate the production of the proinflammatory cytokines IFN-c and TNF-a and the inflammatory chemokine CCL2 (MCP-1) in dose-dependent manners. 25 These effects of GK1, along with other unexplored innate and adaptive immune mechanisms, could at least, in part, explain the observed anti-tumoral effects of this peptide in an experimental murine model of melanoma. Thus, it is feasible to speculate that IFN-c could play a central role in the antitumor effects observed in this study, as IFN-c has been shown to be a mediator of tumor immunity.…”

“…This therapeutic effect could have been related to various immune mechanisms stimulated by GK1, 27 but its precise role as an anti-tumoral molecule remains to be determined. Since GK1 exerts its effects in a dose-dependent manner, and it is rapidly cleared from the body, 25 it has the potential to be used as a primary or adjuvant component of chemotherapeutic cocktails to treat experimental and human cancers. Currently, our group is performing studies to determine whether GK1 induces the same proinflammatory cytokine profiles in mouse melanoma models and whether these effects are dose dependent.…”

“…[19][20][21][22] Recently, DC-based immunotherapy was clinically approved, and it has been used for the treatment of melanoma. 23 Previous studies have shown that GK1, an 18-amino-acid peptide derived from Taeniacrassiceps cysticerci, 24 induces a high level of protection against cysticercosis 25 without the need for an adjuvant. In addition, the subcutaneous coadministration of GK1 with an influenza vaccine (Fluzone Ô ) increased the levels of anti-influenza virus antibodies in aged mice before and after infection.…”

Coadministration of protoxin Cry1Ac from Bacillus thuringiensis with metacestode extract confers protective immunity to murine cysticercosis

“…Several efforts have been attempted to obtain an effective vaccine against cysticercosis. The designs include total protein extracts, partially purified excretion antigens, vaccine peptide synthesis and DNA vaccines (2)(3)(4)(5)(11)(12)(13). But discrepancies regarding the more appropriate antigen type for inducing effective immunity still exist (4,12).…”