Vaccination against the abomasal cattle nematode Ostertagia ostertagi
Background
At present, the control of O. ostertagi and other gastrointestinal nematodes is mainly based on preventive anthelmintic treatment programs. However, the high costs of anthelmintic treatments, the negative effect of preventive anthelmintic treatments on the development of natural immunity against gastrointestinal nematodes, consumer concerns regarding drug residues in food products and in the environment and, last but not least, the increasing incidence of parasite resistance against the available anthelmintics are strong incentives for the producers to adopt alternative control systems. Vaccination is being considered as the most feasible solution. Because nematodes are multicellular organisms that stimulate complex immune responses in their hosts few parasitic vaccines are available until now. Today, the evolution in biotechnology allows the development of new generation' vaccines based on recombinant DNA technology.
Current research
Recent studies in our laboratory demonstrated that vaccination of calves with different O. ostertagi excretory-secretory (ES) proteins, such as the ‘ES thiol fraction’, enriched for ASPs and cysteine proteinases, and a polyprotein allergen (OPA) fraction, can induce a protective immune response against Ostertagia. The protection is reflected in a significant reduction of at least 60 % in faecal egg counts during a two month period after the initial infection. Based on published studies these results can be considered as the highest level of protection induced against O. ostertagi in cattle by vaccination. Further work aims at the identification of the function of these proteins for the parasites by RNAi, the large scale production of the protective antigens as recombinant proteins and optimisation of the antigen delivery to the mucosal immune system in the abomasum. In addition, a number of other potential protective antigens were also identified and are currently being evaluated as vaccine candidates.
Contact
Prof. Dr. E. Claerebout 
Prof. Dr. J. Vercruysse 
Prof. Dr. P. Geldhof 
In collaboration with:
Dr. D. Knox (Moredun Research Institute, Scotland)
Dr. Collette Britton (Glasgow University)
Publications since 2002
Geldhof, P., Claerebout, E., Knox, D.P., Vercauteren, I., Loosova, A., Vercruysse, J., 2002. Vaccination of calves against Ostertagia ostertagi with cysteine proteinase enriched protein fractions. Parasite Immun 24, 263-270.
De Maere, V., Vercauteren, I., Saverwyns, H., Claerebout, E., Berx, G., Vercruysse, J., 2002. Identification of potential protective antigens of Ostertagia ostertagi with local antibody probes. Parasitology 125, 383-391.
Vercauteren, I., Geldhof, P., Peelaers, I., Claerebout, E., Berx, G., Vercruysse, J., 2003. Identification of excretory-secretory products of larval and adult Ostertagia ostertagi by immunoscreening of cDNA libraries. Mol Biochem Parasitol 126, 201-208.
Claerebout, E., Knox, D.P., Vercruysse, J., 2003. Current research and future prospects in the development of vaccines against gastrointestinal nematodes in cattle. Expert Rev Vaccines 2, 147-157.
Geldhof, P., Vercauteren, I., Knox, D.P., De Maere, V., Vanzeveren, A., Berx, G., Vercruysse, J., Claerebout, E., 2003. Protein disulphide isomerase of Ostertagia ostertagi : an excretory-secretory product of L4 and adult worms? Int J Parasitol 33, 129-136.
Geldhof, P., Vercauteren, I., Gevaert K., Staes A., Knox, D.P., Vandekerckhove J., Vercruysse, J., Claerebout, E., 2003. Activation-associated secreted proteins are the most abundant proteins in a host protective fraction of Ostertagia ostertagi. Mol Biochem Parasitol 128, 111-114.
Claerebout, E., Vercruysse, J., 2003. Assessment of the efficacy of helminth vaccines. J Parasitol 89 (Suppl.), pp.S202-S209.
Vercauteren, I., Geldhof, P., Vercruysse, J., Peelaers, I., Van Den Broeck, W., Gevaert, K., Claerebout, E., 2004. Vaccination with an Ostertagia polyprotein allergen protects calves against a homologous challenge infection. Infect Immun 72(5), 2995-3001.
Geldhof, P., Vercauteren, I., Vercruysse, J., Knox, D.P., Van Den Broeck, W., Claerebout, E., 2004. Validation of the protective capacity of the Ostertagia ostertagi ES-thiol antigens with different adjuvantia. Parasite Immun 26, 37-43.
De Maere, V., Vercauteren, I., Geldhof, P., Gevaert K., Vercruysse, J., Claerebout, E., 2005. Molecular analysis of astacin-like metalloproteases of Ostertagia ostertagi. Parasitology 130, 89-98.
Claerebout, E., Smith, W.D., Pettit, D., Geldhof, P., Raes, S., Geurden, T., Vercruysse, J., 2005. Protection studies with a globin-enriched protein fraction of Ostertagia ostertagi. Vet Parasitol 128, 299-307.
De Maere, V., Vercauteren, I., Gevaert K., Vercruysse, J., Claerebout, E., 2005. An aspartyl protease inhibitor of Ostertagia ostertagi: Molecular cloning, analysis of stage and tissue specific expression and vaccine trial. Mol Biochem Parasitol 141, 81-88.
Claerebout, E., Vercauteren, I., Geldhof, P., Olbrechts, A., Zarlenga, D.S., Goddeeris, B., Vercruysse, J., 2005. Cytokine responses in immunised and non-immunised calves after Ostertagia ostertagi infection. Parasite Immun 27, 325-331.
Visser, A., Geldhof, P., De Maere, V., Knox, D.P., Vercruysse, J., Claerebout, E., 2006. Efficacy and specificity of RNA interference in larval life stages of Ostertagia ostertagi. Parasitology 133, 777-783.
Vercauteren, I., De Maere, V., Vercruysse, J., Stevens, M., Gevaert, K., Claerebout, E., 2006. A small heat shock protein of Ostertagia ostertagi: stage- and tissue-specific expression, heat inducibility and protection trial. J Parasitol 92, 1244-1250.
Geldhof, P., Visser, A., Clark, D., Saunders, G., Britton, C., Gilleard, J., Berriman, M., Knox, D., 2007. RNA interference in parasitic helminths: current situation, potential pitfalls and future prospects. Parasitology (in press).
Knox, D.P., Geldhof, P., Visser, A., Britton, C., 2007. RNA interference in parasitic nematodes: A reality check? Trends Parasitol (In press).
Meyvis, Y., Geldhof, P., Gevaert K., Timmerman, E., Vercruysse, J., Claerebout, E., 2007. Vaccination against Ostertagia ostertagi with subfractions of the protective ES-thiol fraction. Vet Parasitol 149, 239-345.
Saverwyns, H., Visser, A., Nisbet, A., Peelaers, I., Gevaert, K., Vercruysse, J., Claerebout, E. and Geldhof, P., 2007. Identification and characterization of a novel specific secreted protein family for selected members of the subfamily Ostertagiinae (Nematoda). Parasitology135, 63-70
Vercruysse J., Schetters T.P.M., Knox D.P., Willadsen P., Claerebout E., 2007. Control of parasitic disease using vaccines: an answer to drug resistance? Revue Scientifique et Technique-Office International des Epizooties 26, 105-115.
Geldhof P., De Maere V., Vercruysse J., Claerebout E., 2007. Recombinant expression systems: the obstacle to helminth vaccines? Trends Parasitol 23, 527-532.
Geldhof P., Meyvis Y., Vercruysse J., Claerebout E. 2008. Vaccine testing of a recombinant activation-associated secreted protein (ASP1) from Ostertagia ostertagi. Parasite Immunol 30, 57-60
Visser A., Van Zeveren A.M., Meyvis Y., Peelaers I., Van den Broeck W., Gevaert K., Vercruysse J., Claerebout E., Geldhof P., 2008. Gender-enriched transcription of activation associated secreted proteins in Ostertagia ostertagi. Int J Parasitol 38, 455-465
Meyvis Y., Callewaert N., Gevaert K., Timmerman E., Van Durme J., Schymkowitz J., Rousseau F., Vercruysse J., Claerebout E., Geldhof P., 2008. Hybrid N-glycans on the host protective activation-associated secreted proteins of Ostertagia ostertagi and their importance in immunogenicity. Mol Biochem Parasitol 161, 67-71.
Saverwyns, H., Visser, A., Van Durme, J., Power, D., Morgado, I., Kennedy, M.W., Knox, D.P., Schymkowitz, J., Rousseau, F., Gevaert, K., Vercruysse, J., Claerebout, E., Geldhof, P., 2008. Analysis of the transthyretin like (TTL) gene family in Ostertagia ostertagi – comparison with other strongylid nematodes and Caenorhabditis elegans. Int J Parasitol 38, 1545-1556
Meyvis, Y., Houthoofd, W., Visser, A., Borgonie, G., Gevaert, K., Vercruysse, J., Claerebout, E., Geldhof, P., 2009. Analysis of the translationally controlled tumor protein in the nematoda Ostertagia ostertagi and Caenorhabditis elegans suggests a pivotal role in egg production. Int J Parasitol 39,1205-1213