Glycobiology Advance Access originally published online on August 7, 2003
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Glycobiology, 2003, Vol. 13, No. 11 795-804
© 2003 Oxford University Press
Vaccination-induced protection of lambs against the parasitic nematode Haemonchus contortus correlates with high IgG antibody responses to the LDNF glycan antigen
2 Utrecht University, Department of Infectious Diseases and Immunology, Division of Parasitology and Tropical Veterinary Medicine, PO Box 80.165, 3508 TD Utrecht, The Netherlands; 3 VU University Medical Center, Department of Molecular Cell Biology and Immunology, Glycoimmunology Group, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands; and 4 University of Oklahoma Health Sciences Center, Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, Oklahoma City, OK 73104
Received on June 20, 2003; revised on July 14, 2003; accepted on July 17, 2003
Lambs respond to vaccination against bacteria and viruses 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 immunized with ES in Alhydrogel and challenged with 300 L3 larvae/kg body weight had a reduction in cumulative egg output of 89% and an increased percentage protection of 54% compared with 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 GalNAcß1,4 (Fuc
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 immunization onward and was significantly higher in protected lambs. In addition, an isotype switch from LDNF-specific IgM to IgG was induced that 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 aluminum adjuvant. This combination generated high and specific antiglycan antibody responses that may contribute to the vaccination-induced protection.
1 To whom correspondence should be addressed; e-mail: l.vervelde{at}vet.uu.nl
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