|VAN MEULDER, F - Ghent University|
|RATMAN, D - Ghent University|
|VAN COPPERNOLLE, S - Ghent University|
|BORLOO, J - Ghent University|
|CHIERS, K - Ghent University|
|VAN DEN BROECK, W - Ghent University|
|CLAEREBOUT, E - Ghent University|
|GELDHOF, P - Ghent University|
Submitted to: International Journal for Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/24/2015
Publication Date: 5/1/2015
Citation: Van Meulder, F., Ratman, D., Van Coppernolle, S., Borloo, J., Li, R.W., Chiers, K., Van Den Broeck, W., Claerebout, E., Geldhof, P. 2015. Analysis of the protective immune response following intramuscular vaccination of calves against the intestinal parasite Cooperia oncophora. International Journal for Parasitology. pii:S0020-7519(15)00112-5. DOI: 10.1016/j.ijpara.2015.03.007.
Interpretive Summary: The intestinal worm Cooperia oncophora is one of the most prevalent cattle parasites. Rapid emergence of drug-resistant parasite strains calls for the development of optimal vaccines. A vaccine developed using a double domain activation-associated secreted protein significantly reduced parasite egg output by 91%, increased the number of inhibited larvae, and decreased total worm counts. In this study, we attempted to understand the immune mechanisms involved in the vaccine-induced protection. Our results will undoubtedly facilitate the development of more effective vaccines against the internal parasite.
Technical Abstract: Anthelmintic resistance in the bovine parasite Cooperia oncophora is developing and spreading rapidly worldwide. Vaccination is therefore often put forward as a cost-effective alternative for chemical drugs. Recently we reported the successful evaluation of a double domain activation-associated secreted protein, purified from the excretory-secretory material of adult stage parasites, to induce high levels of protection against a challenge infection following vaccination. In an attempt to elucidate the immune mechanisms involved, both the humoral and cell-mediated immune responses following vaccination and infection were analyzed and compared with non-vaccinated control animals. Antigen-specific IgG1, IgG2 and IgA levels were significantly increased in serum of vaccinated animals post vaccination, whereas no effect was observed for IgM. Antigen specific mucosal IgG1 levels were significantly increased in the vaccinated animals, whereas no differences were observed for antigen-specific IgA, IgM and IgG2 levels. Upon re-stimulation with the vaccine antigen, a significant proliferation of both aß- and 'd-T-cells and B-cells, collected from mesenteric lymphnodes, was only observed in vaccinated animals. Finally, an RNA-seq analysis on mucosal tissue yielded a list of 67 genes that were differentially expressed in vaccinated animals following challenge infection, amongst which were several cell adhesion molecules, lectins and glycosyl transferases. A correlation analysis between all immunological and parasitological parameters indicated that mucosal anti-Cooperia IgG1 levels correlated negatively with cumulative faecal egg counts and positively with the number of L4 and L5 larvae. The number of larvae were also positively correlated with the proliferation of aß T-cells. Worm length was negatively correlated with the transcript levels of several lectins and cell adhesion molecules. Overall, the results indicate that intramuscular administration of the vaccine resulted in a mucosal immune memory response particularly characterized by increased antigen-specific IgG1 levels in the intestinal mucosa.