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Stimulation of innate immunity in newborn kids against Cryptosporidium parvum infection-challenge by intranasal/per-oral administration of liposomal formulation of N-L18-norAbu-GMDP adjuvant

Published online by Cambridge University Press:  01 July 2005

J. TURÁNEK ,
A. KAšNÁ ,
B. KOUDELA ,
M. LEDVINA  and
A. D. MILLER
J. TURÁNEK
Affiliation:
Veterinary Research Institute, Hudcova 70, 62132 Brno, Czech Republic
A. KAšNÁ
Affiliation:
Veterinary Research Institute, Hudcova 70, 62132 Brno, Czech Republic
B. KOUDELA
Affiliation:
University of Veterinary and Pharmaceutical Sciences, Palackého 1-3, 61242 Brno, Czech Republic Institute of Parasitology, Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic
M. LEDVINA
Affiliation:
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 16610 Prague, Czech Republic
A. D. MILLER
Affiliation:
Imperial College Genetic Therapies Centre, Department of Chemistry, Flowers Building, Armstrong Road, Imperial College London, London, SW7 2AZ, UK; IC-Vec Ltd, Flowers Building, Armstrong Road, London, SW7 2AZ, UK
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Abstract

The effects of a liposomal preparation of lipophilic immunomodulator β-D-GlcNstearoyl-(1-4)-norMurNAc-L-Abu-D-isoGln (N-L18-norAbu-GMDP) were investigated on resistance to Cryptosporidium parvum infection in neonatal kids. The liposomal preparation was administered subcutaneously or intranasally/orally (i.n./p.o.) twice at doses of 100 μg, 200 μg, or 1000 μg per kid pre-infection challenge. The treatment schemes were (i) 72 and 24 h pre-infection challenge, (ii) 24 h pre-infection challenge and 24 h post-infection challenge (oral inoculation with 1×107 oocysts of C. parvum in 5 ml of PBS). Administration of liposomal N-L18-norAbu-GMDP by i.n./p.o. route at the cumulative dose of 2000 μg per kid 72 and 24 h pre-infection challenge, lead to substantially increased clearance of coccidian parasites from various parts of the intestine. On the basis of histological examination, the distribution of cryptosporidia in the intestine and the severity of the infection, treated kids were classified on day 5 as having a strong reduction in infection in comparison to the control group (P<0·05). No cryptosporidia were found on the mucosal surface of treated kids by day 10, while the intestines of the control kids were still infected. All doses and routes of administration were judged effective with respect to suppression of cryptosporidia infections.

Keywords

Cryptosporidium parvumimmunomodulationliposomesmuramyldipeptidemuramyldipeptide analoguesgoatβ-D-GlcNstearoyl-(1-4)-norMurNAc-L-Abu-D-isoGlnN-L18-norAbu-GMDP
Type
Research Article
Information
Parasitology , Volume 131 , Issue 5 , November 2005 , pp. 601 - 608
Copyright
© 2005 Cambridge University Press

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References

REFERENCES

Adam, A. and Lederer, E. ( 1984). Muramylpeptides, immunomodulators, sleep factors and vitamins. Medicinal Research Reviews 4, 111–152.CrossRefGoogle Scholar
Barratt, G. and Morin, C. ( 1995) Liposomal immunomodulators. In Liposomes, New Systems and New Trends in their Applications (ed. Puisieux, F., Couvreur, P., Delattre, J. and Devissaguet, J. P.), pp. 461–506. Scientific Publications, Paris.
Childers, N. K., Denis, F. R., McGee, N. F. and Michalek, S. M. ( 1990). Ultrastructural study of liposome uptake by M cells of rat Peyer's path, an oral vaccine system for delivery of purified antigen. Regional Immunology 3, 8–16.Google Scholar
De Graaf, D. C., Sspano, F., Petry, F., Sagodira, S. and Bonnin, A. ( 1999 b). Speculation on whether a vaccine against cryptosporidiosis is a reality or fantasy. International Journal for Parasitology 29, 1289–1306.Google Scholar
De Graaf, D. C., Vanopdenbosch, E., Ortega-Mora, L. M., Abbassi, H. and Peeters, J. E. ( 1999 a). A review of the importance of cryptosporidiosis in farm animals. International Journal for Parasiotology 29, 1269–1287.Google Scholar
Fogler, W. E. and Fidler, I. J. ( 1986). The activation of tumoricidal properties in human blood monocytes by muramyl peptides requires a specific intracellular interaction. Journal of Immunology 136, 2311–7.Google Scholar
Hockertz, S., Franke, G., Paulini, I. and Lohmann-Matthes, M. L. ( 1991). Immunotherapy of murine visceral leishmaniasis with murine recombinant interferon-γ and MTPPE encapsulated in liposomes. Journal of Interferon Research 11, 177–185.CrossRefGoogle Scholar
Koudela, B. and Vítovec, J. ( 1997). Experimental cryptosporidiosis in kids. Veterinary Parasitology 71, 273–281.CrossRefGoogle Scholar
Krahenbuhl, J. L., Sharma, S. D., Ferraresi, R. W. and Remington, J. S. ( 1981). Effects of muramyl dipeptide treatment on resistance to infection with Toxoplasma gondii in mice. Infection and Immunity 31, 716–722.Google Scholar
Ledvina, M., Zýka, D., Ježek, J., Trnka, T. and šaman, D. ( 1998). New effective synthesis of (N-acetyl- and N-stearoyl-2-amino-2-deoxy-beta-D-glucopyranosyl)-(1–>4)-muramoyl-L-2-aminobutanoyl-D-isoglutamine, analogs of GMDP with immunopotentiating activity. Collection of Czechoslovak Chemical Communications 63, 577–589.CrossRefGoogle Scholar
McDonald, V. ( 1999). Gut intraepithelial lymphocytes and immunity to coccidia. Parasitology Today 15, 483–487.CrossRefGoogle Scholar
McDonald, V. ( 2000). Host cell-mediated responses to infection with Cryptosporidium. Parasite Immunology 22, 597–604.CrossRefGoogle Scholar
O'Donoghue, P. ( 1995). Cryptosporidium and cryptosporidiosis in man and animals. International Journal for Parasitology 25, 139–195.CrossRefGoogle Scholar
Oussoren, CH. and Storm, G. ( 2001). Liposomes to target the lymphatics by subcutaneous administration. Advanced Drug Delivery Reviews 50, 143–156.CrossRefGoogle Scholar
Turánek, J. ( 1994). Fast-protein liquid chromatography system as a tool for liposome preparation by the extrusion procedure. Analytical Biochemistry 218, 352–357.CrossRefGoogle Scholar
Turánek, J., Kašná, A., Záluská, D. and Neča, J. ( 2003). Preparation of sterile liposomes by the proliposome – liposome method. Methods in Enzymology 367, 111–129.CrossRefGoogle Scholar
Yun, Ch-H., Estrada, A., Van Kessel, A., Gajahar, A., Redmond, M. and Laarveld, B. ( 1998) Immunomodulatory effects of oat β-glucan administered intragastrically or parenterally on mice infected with Eimeria vermiformis. Microbiology and Immunology 42, 457–465.Google Scholar