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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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