Design of a Peptide-Carrier Vaccine Based on the Highly Immunogenic Fasciola hepatica Leucine Aminopeptidase

ABSTRACT The liver fluke Fasciola hepatica parasitizes humans and ruminant livestock worldwide, and it is now being considered a reemerging zoonotic disease, especially in areas in which it is endemic, such as South America. This study investigates the immune response to excretory and secretory products produced by F. hepatica in a group of patients from the Peruvian Altiplano, where the disease is highly endemic. Using a proteomic approach and immunoblotting techniques, we have identified the enzymes leucine aminopeptidase (LAP) and phosphoenolpyruvate carboxykinase as immunodominant antigens recognized by sera from fasciolosis patients. An indirect enzyme-linked immunosorbent assay using recombinant LAP as the antigen was developed to check sera from individuals of this region. Our results demonstrate that LAP produces a specific and strong reaction, suggesting its potential use in the serologic diagnosis of F. hepatica infections in humans.

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The recombinant gut-associated M17 leucine aminopeptidase in combination with different adjuvants confers a high level of protection against Fasciola hepatica infection in sheep

Vaccine ◽

10.1016/j.vaccine.2011.09.020 ◽

2011 ◽

Vol 29 (48) ◽

pp. 9057-9063 ◽

Cited By ~ 45

Author(s):

Gabriela Maggioli ◽

Daniel Acosta ◽

Fernando Silveira ◽

Silvina Rossi ◽

Sheila Giacaman ◽

...

Keyword(s):

Leucine Aminopeptidase ◽

Fasciola Hepatica ◽

Hepatica Infection ◽

High Level

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Construction and evaluation of a chimeric protein made fromFasciola hepaticaleucine aminopeptidase and cathepsin L1

Journal of Helminthology ◽

10.1017/s0022149x14000686 ◽

2014 ◽

Vol 90 (1) ◽

pp. 7-13 ◽

Cited By ~ 3

Author(s):

K. Hernández-Guzmán ◽

A. Sahagún-Ruiz ◽

A.J. Vallecillo ◽

I. Cruz-Mendoza ◽

H. Quiroz-Romero

Keyword(s):

Escherichia Coli ◽

Amino Acids ◽

Western Blot ◽

Specific Antibody ◽

Diagnostic Tool ◽

Leucine Aminopeptidase ◽

Fasciola Hepatica ◽

Chimeric Protein ◽

Antibody Responses ◽

Immunogenic Properties

AbstractLeucine aminopeptidase (LAP) and cathepsin L1 (CL1) are important enzymes for the pathogenesis and physiology ofFasciola hepatica. These enzymes were analysedin silicoto design a chimeric protein containing the most antigenic sequences of LAP (GenBank; AAV59016.1; amino acids 192–281) and CL1 (GenBank CAC12806.1; amino acids 173–309). The cloned 681-bp chimeric fragment (rFhLAP-CL1) contains 270 bp from LAP and 411 bp from CL1, comprising three epitopes, DGRVVHLKY (amino acids 54–62) from LAP, VTGYYTVHSGSEVELKNLV (amino acids 119–137) and YQSQTCLPF (amino acids 161–169) from CL1. The ~25 kDa rFhLAP-CL1 chimeric protein was expressed from the pET15b plasmid in the Rosetta (DE3)Escherichia colistrain. The chimeric protein rFhLAP-CL1, which showed antigenic and immunogenic properties, was recognized in Western blot assays usingF. hepatica-positive bovine sera, and induced strong, specific antibody responses following immunization in rabbits. The newly generated chimeric protein may be used as a diagnostic tool for detection of antibodies againstF. hepaticain bovine sera and as an immunogen to induce protection against bovine fasciolosis.

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Fasciolosis in South America: epidemiology and control challenges

Journal of Helminthology ◽

10.1017/s0022149x16000560 ◽

2016 ◽

Vol 91 (2) ◽

pp. 99-109 ◽

Cited By ~ 19

Author(s):

C. Carmona ◽

J.F. Tort

Keyword(s):

South America ◽

Leucine Aminopeptidase ◽

Fasciola Hepatica ◽

Production Systems ◽

Single Antigen ◽

Growing Body ◽

Livestock Farmers ◽

And Control ◽

Thioredoxin Glutathione Reductase

AbstractFasciolosis caused byFasciola hepaticaseverely affects the efficiency of livestock production systems worldwide. In addition to the economic impact inflicted on livestock farmers, fasciolosis is an emergent zoonosis. This review emphasizes different aspects of the disease in South America. Available data on epidemiology in bovines and ovines in different countries, as well as a growing body of information on other domestic and wildlife definitive hosts, are summarized. The issue of drug resistance that compromises the long-term sustainability of current pharmacological strategies is examined from a regional perspective. Finally, efforts to develop a single-antigen recombinant vaccine in ruminants are reviewed, focusing on the cases of leucine aminopeptidase or thioredoxin glutathione reductase.

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Characterization and Partial Purification of a Leucine Aminopeptidase from Fasciola hepatica

Journal of Parasitology ◽

10.2307/3284518 ◽

1998 ◽

Vol 84 (1) ◽

pp. 1 ◽

Cited By ~ 42

Author(s):

Daniel Costa ◽

Fernando Goni ◽

Carlos Carmona

Keyword(s):

Leucine Aminopeptidase ◽

Fasciola Hepatica ◽

Partial Purification

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Fasciola hepatica leucine aminopeptidase, a promising candidate for vaccination against ruminant fasciolosis☆

Molecular and Biochemical Parasitology ◽

10.1016/j.molbiopara.2007.11.011 ◽

2008 ◽

Vol 158 (1) ◽

pp. 52-64 ◽

Cited By ~ 62

Author(s):

Daniel Acosta ◽

Martín Cancela ◽

Lucia Piacenza ◽

Leda Roche ◽

Carlos Carmona ◽

...

Keyword(s):

Leucine Aminopeptidase ◽

Fasciola Hepatica ◽

Promising Candidate ◽

Aminopeptidase A

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Fasciolaantigens as vaccines against fascioliasis and schistosomiasis

Journal of Helminthology ◽

10.1079/joh2005304 ◽

2005 ◽

Vol 79 (3) ◽

pp. 241-247 ◽

Cited By ~ 71

Author(s):

G.V. Hillyer

Keyword(s):

Fatty Acid Binding Protein ◽

Leucine Aminopeptidase ◽

Fasciola Hepatica ◽

Protective Effects ◽

Fatty Acid Binding ◽

Vaccine Candidates ◽

Acid Binding Protein ◽

Cathepsin Proteases ◽

Cysteine Cathepsin ◽

Potential Vaccine

AbstractFascioliasis is an important trematode infection of herbivores worldwide with increasing evidence of prevalence as a disease of humans. Vaccination studies with purified native and recombinantFasciolaantigens suggest that this approach to diminished morbidity and mortality and reduced transmission is a realistic goal. Among the major potential vaccine candidates are fatty acid binding protein (FABP), cysteine (cathepsin) proteases, haemoglobulin, leucine aminopeptidase, and a saposin-like protein. In the case ofFasciola hepaticaFABP, cross-reaction and cross-protection againstSchistosoma mansoniis an important feature. In addition to protective effects with significant worm burden reductions, some vaccine candidates also have anti-fecundity (smaller flukes), anti-pathology (less liver lesions), and anti-embryonation effects. Optimism is tempered by the fact that fascioliasis in humans is an orphan disease and in need of governmental and foundation support.

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