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Glycobiology Advance Access published online on August 7, 2003
Glycobiology, doi:10.1093/glycob/cwg107
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Submitted on June 20, 2003
Revised on July 14, 2003
Accepted on July 17, 2003

© 2003 Oxford University Press

ORIGINAL ARTICLES

Vaccination induced protection of lambs against the parasitic nematode Haemonchus contortus correlates with high IgG antibody responses to the LDNF glycan antigen

Lonneke Vervelde 1*, Nicole Bakker 1, Frans N. J. Kooyman 1, Albert W. C. A. Cornelissen 1, Christine M. C. Bank 2, A. Kwame Nyame 3, Richard D. Cummings 3, and Irma van Die 2

1 Utrecht University, Department of Infectious Diseases and Immunology, Division of Parasitology & Tropical Veterinary Medicine, PO Box 80.165, 3508 TD Utrecht, The Netherlands
2 VU University Medical Center, Department of Molecular Cell Biology & Immunology, Glycoimmunology Group, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
3 University of Oklahoma Health Sciences Center, Dept. of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, Oklahoma City, Oklahoma 73104, USA

* To whom correspondence should be addressed. E-mail: L.Vervelde{at}vet.uu.nl.

Abstract

Lambs respond to vaccination against bacteria and virusses, but have a poor immunological response to nematodes. Here we report that they are protected against the parasitic nematode Haemonchus contortus after vaccination with excretory/secretory (ES) glycoproteins using Alhydrogel as an adjuvant. Lambs immunised with ES in Alhydrogel and challenged with 300 L3 larvae/kg bodyweight had a reduction in cumulative egg output of 89% and an increased percentage protection of 54% compared to the adjuvant control group. Compared to the adjuvant dimethyl dioctadecyl ammonium bromide, Alhydrogel induced earlier onset and significantly higher ES-specific IgG, IgA and IgE antibody responses. In all vaccinated groups a substantial proportion of the antibody response was directed against glycan epitopes, irrespective of the adjuvant used. In lambs vaccinated with ES in Alhydrogel, but not in any other group, a significant increase was found in antibody levels against the GalNAc{beta}1,4(Fuc{alpha}1,3)GlcNAc (fucosylated LacdiNAc, LDNF) antigen, a carbohydrate antigen that is also involved in the host defense against the human parasite Schistosoma mansoni. In lambs the LDNF-specific response increased from the first immunisation onwards and was significantly higher in protected lambs. In addition, an isotype switch from LDNF-specific IgM to IgG was induced which correlated with protection. These data demonstrate that hyporesponsiveness of lambs to H. contortus can be overcome by vaccination with ES glycoproteins in a strong T-helper 2 type response-inducing aluminium adjuvant. This combination generated high and specific anti-glycan antibody responses that may contribute to the vaccination-induced protection.


carbohydrate-specific antibody response, excretory-secretory products, Haemonchus, N-glycans, vaccine, fucosylated LacdiNAc
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