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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

Phase contrast and fluorescent microscopy of Cryptobia salmositica after exposure to isometamidium chloride. (a): Exposure to drug only, note accumulation of drug (in red) in the kinetoplast; (b):  exposure to drug conjugated to polyclonal antibodies from a recovered fish, note that the drug (in red) is throughout the organism (reproduced from Ardelli and Woo [59]).
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fig9: Phase contrast and fluorescent microscopy of Cryptobia salmositica after exposure to isometamidium chloride. (a): Exposure to drug only, note accumulation of drug (in red) in the kinetoplast; (b): exposure to drug conjugated to polyclonal antibodies from a recovered fish, note that the drug (in red) is throughout the organism (reproduced from Ardelli and Woo [59]).

Mentions: Ardelli and Woo [59] conjugated isometamidium chloride to polyclonal antibodies (from “recovered” fish) and the monoclonal antibody (mAb-001, Section 3.1). The conjugated drug is on the entire parasite while the unconjugated drug accumulates only in the kinetoplast (Figure 9). Before drug conjugation both antibodies agglutinate living parasites but they react differently after drug conjugation. Polyclonal antibodies-conjugated drug (PAIC) lyses most of the parasite and it no longer agglutinates the parasite. In contrast, the mAb-00-conjugated drug does not lyse C. salmositica but agglutinates it. After in vitro exposure to PAIC the infectivity of the parasite and subsequent parasitaemias in inoculated fish were significantly lowered. Fish survival (Table 1) was much higher in juvenile chinook salmon infected with parasites exposed to the polyclonal antibodies-conjugated drug (PAIC) than to drug alone (Drug) or to polyclonal antibodies alone (Antibody) or to drug plus polyclonal antibody (PAI). Also, preliminary studies indicate the drug-antibody conjugate to be effective when injected into infected fish. The results are encouraging and further studies are needed, for example, to determine dosages needed, refinement of the approach (e.g., stage of infection, species of salmonids).


Immunological and therapeutic strategies against salmonid cryptobiosis.

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

Phase contrast and fluorescent microscopy of Cryptobia salmositica after exposure to isometamidium chloride. (a): Exposure to drug only, note accumulation of drug (in red) in the kinetoplast; (b):  exposure to drug conjugated to polyclonal antibodies from a recovered fish, note that the drug (in red) is throughout the organism (reproduced from Ardelli and Woo [59]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig9: Phase contrast and fluorescent microscopy of Cryptobia salmositica after exposure to isometamidium chloride. (a): Exposure to drug only, note accumulation of drug (in red) in the kinetoplast; (b): exposure to drug conjugated to polyclonal antibodies from a recovered fish, note that the drug (in red) is throughout the organism (reproduced from Ardelli and Woo [59]).
Mentions: Ardelli and Woo [59] conjugated isometamidium chloride to polyclonal antibodies (from “recovered” fish) and the monoclonal antibody (mAb-001, Section 3.1). The conjugated drug is on the entire parasite while the unconjugated drug accumulates only in the kinetoplast (Figure 9). Before drug conjugation both antibodies agglutinate living parasites but they react differently after drug conjugation. Polyclonal antibodies-conjugated drug (PAIC) lyses most of the parasite and it no longer agglutinates the parasite. In contrast, the mAb-00-conjugated drug does not lyse C. salmositica but agglutinates it. After in vitro exposure to PAIC the infectivity of the parasite and subsequent parasitaemias in inoculated fish were significantly lowered. Fish survival (Table 1) was much higher in juvenile chinook salmon infected with parasites exposed to the polyclonal antibodies-conjugated drug (PAIC) than to drug alone (Drug) or to polyclonal antibodies alone (Antibody) or to drug plus polyclonal antibody (PAI). Also, preliminary studies indicate the drug-antibody conjugate to be effective when injected into infected fish. The results are encouraging and further studies are needed, for example, to determine dosages needed, refinement of the approach (e.g., stage of infection, species of salmonids).

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