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Immunological and therapeutic strategies against salmonid cryptobiosis.

Woo PT - J. Biomed. Biotechnol. (2009)

Bottom Line: MAb-001 does not fix complement but agglutinates the parasite.Complement fixing antibody production and cell-mediated response in vaccinated fish rise significantly after challenge.Isometamidium chloride is therapeutic against the pathogen and its effectiveness is increased after conjugation to antibodies.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Biology, University of Guelph, Guelph, ON, Canada.

ABSTRACT
Salmonid cryptobiosis is caused by the haemoflagellate, Cryptobia salmositica. Clinical signs of the disease in salmon (Oncorhynchus spp.) include exophthalmia, general oedema, abdominal distension with ascites, anaemia, and anorexia. The disease-causing factor is a metalloprotease and the monoclonal antibody (mAb-001) against it is therapeutic. MAb-001 does not fix complement but agglutinates the parasite. Some brook charr, Salvelinus fontinalis cannot be infected (Cryptobia-resistant); this resistance is controlled by a dominant Mendelian locus and is inherited. In Cryptobia-resistant charr the pathogen is lysed via the Alternative Pathway of Complement Activation. However, some charr can be infected and they have high parasitaemias with no disease (Cryptobia-tolerant). In infected Cryptobia-tolerant charr the metalloprotease is neutralized by a natural antiprotease, alpha2 macroglobulin. Two vaccines have been developed. A single dose of the attenuated vaccine protects 100% of salmonids (juveniles and adults) for at least 24 months. Complement fixing antibody production and cell-mediated response in vaccinated fish rise significantly after challenge. Fish injected with the DNA vaccine initially have slight anaemias but they recover and have agglutinating antibodies. On challenge, DNA-vaccinated fish have lower parasitaemias, delayed peak parasitaemias and faster recoveries. Isometamidium chloride is therapeutic against the pathogen and its effectiveness is increased after conjugation to antibodies.

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Related in: MedlinePlus

Ultrastructural lesions in Cryptobia salmositica after in vitro exposure to isometamidium chloride. (a) Parasite kinetoplast (K) not exposed to the drug; (b) condensation of kinetoplast DNA after exposure to the drug; (c) vacuole (V) formation after drug exposure; (d) swelling of mitochondrial cristae (C) after drug exposure; (e) vacuole formation in cytoplasm after drug exposure (reproduced from Ardelli and Woo [44]).
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fig8: Ultrastructural lesions in Cryptobia salmositica after in vitro exposure to isometamidium chloride. (a) Parasite kinetoplast (K) not exposed to the drug; (b) condensation of kinetoplast DNA after exposure to the drug; (c) vacuole (V) formation after drug exposure; (d) swelling of mitochondrial cristae (C) after drug exposure; (e) vacuole formation in cytoplasm after drug exposure (reproduced from Ardelli and Woo [44]).

Mentions: Samorin accumulates rapidly in the kinetoplast of the parasite [44], causes condensation of its kinetoplast DNA, forms vacuoles, and swells the mitochondrial cristae (Figure 8). Although the parasite normally undergoes aerobic respiration [25], it also has glycolytic enzymes sequestered in microbodies called glycosomes [58]. The in vitro oxygen consumption and carbon dioxide production decrease significantly after drug exposure with very significant increases in secretion of glycolytic products (lactate and pyruvate) as the parasite switches from aerobic respiration to glycolysis after its mitochondrion is damaged by the drug [44]. Also, in vitro exposure to sublethal levels of the drug reduces infectivity of the parasite to fish and changes the surface glycoprotein antibody-receptor sites of the parasite. This alteration of surface epitopes explains the protection of some parasites from lysis by complement fixing antibodies when rainbow trout with acute infections were treated with the drug [56].


Immunological and therapeutic strategies against salmonid cryptobiosis.

Woo PT - J. Biomed. Biotechnol. (2009)

Ultrastructural lesions in Cryptobia salmositica after in vitro exposure to isometamidium chloride. (a) Parasite kinetoplast (K) not exposed to the drug; (b) condensation of kinetoplast DNA after exposure to the drug; (c) vacuole (V) formation after drug exposure; (d) swelling of mitochondrial cristae (C) after drug exposure; (e) vacuole formation in cytoplasm after drug exposure (reproduced from Ardelli and Woo [44]).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801003&req=5

fig8: Ultrastructural lesions in Cryptobia salmositica after in vitro exposure to isometamidium chloride. (a) Parasite kinetoplast (K) not exposed to the drug; (b) condensation of kinetoplast DNA after exposure to the drug; (c) vacuole (V) formation after drug exposure; (d) swelling of mitochondrial cristae (C) after drug exposure; (e) vacuole formation in cytoplasm after drug exposure (reproduced from Ardelli and Woo [44]).
Mentions: Samorin accumulates rapidly in the kinetoplast of the parasite [44], causes condensation of its kinetoplast DNA, forms vacuoles, and swells the mitochondrial cristae (Figure 8). Although the parasite normally undergoes aerobic respiration [25], it also has glycolytic enzymes sequestered in microbodies called glycosomes [58]. The in vitro oxygen consumption and carbon dioxide production decrease significantly after drug exposure with very significant increases in secretion of glycolytic products (lactate and pyruvate) as the parasite switches from aerobic respiration to glycolysis after its mitochondrion is damaged by the drug [44]. Also, in vitro exposure to sublethal levels of the drug reduces infectivity of the parasite to fish and changes the surface glycoprotein antibody-receptor sites of the parasite. This alteration of surface epitopes explains the protection of some parasites from lysis by complement fixing antibodies when rainbow trout with acute infections were treated with the drug [56].

Bottom Line: MAb-001 does not fix complement but agglutinates the parasite.Complement fixing antibody production and cell-mediated response in vaccinated fish rise significantly after challenge.Isometamidium chloride is therapeutic against the pathogen and its effectiveness is increased after conjugation to antibodies.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Biology, University of Guelph, Guelph, ON, Canada.

ABSTRACT
Salmonid cryptobiosis is caused by the haemoflagellate, Cryptobia salmositica. Clinical signs of the disease in salmon (Oncorhynchus spp.) include exophthalmia, general oedema, abdominal distension with ascites, anaemia, and anorexia. The disease-causing factor is a metalloprotease and the monoclonal antibody (mAb-001) against it is therapeutic. MAb-001 does not fix complement but agglutinates the parasite. Some brook charr, Salvelinus fontinalis cannot be infected (Cryptobia-resistant); this resistance is controlled by a dominant Mendelian locus and is inherited. In Cryptobia-resistant charr the pathogen is lysed via the Alternative Pathway of Complement Activation. However, some charr can be infected and they have high parasitaemias with no disease (Cryptobia-tolerant). In infected Cryptobia-tolerant charr the metalloprotease is neutralized by a natural antiprotease, alpha2 macroglobulin. Two vaccines have been developed. A single dose of the attenuated vaccine protects 100% of salmonids (juveniles and adults) for at least 24 months. Complement fixing antibody production and cell-mediated response in vaccinated fish rise significantly after challenge. Fish injected with the DNA vaccine initially have slight anaemias but they recover and have agglutinating antibodies. On challenge, DNA-vaccinated fish have lower parasitaemias, delayed peak parasitaemias and faster recoveries. Isometamidium chloride is therapeutic against the pathogen and its effectiveness is increased after conjugation to antibodies.

Show MeSH
Related in: MedlinePlus