AnaVac - Transformed Anaplasma Phagocytophilum

The tick-borne bacterium Anaplasma phagocytophilum causes severe disease in sheep and estimates show that approximately 300.000-400.000 lambs are infected annually. Vaccines against A. phagocytophilum are currently not available. Prophylaxis is mostly done by a variety of pour-on applications and long-acting tetracycline has also been used as a prophylactic measure. However, there is a growing concern about the environmental safety and human health and emerging antibiotic and antiparasitic resistance in target- and non-target organisms. The main aim of this project is to find an effective immunizing agent against the highly virulent and prevalent bacterium to improve the welfare of sheep and to reduce the use of chemicals and antibiotics. The project will identify vaccine candidates by immunizing lambs with an attenuated strain of A. phagocytophilum. The attenuation is made by transformation of the bacterium by random transposon mutagenesis. The method allows interruption of essential genes that regulate the virulence of the organism. The research hypothesis is that we can use these transformed bacteria to generate a subclinical infection that allows stimulation of the immune system. Safety measures are important to avoid the intentional or unintentional spread of the organism as well as the protection of personnel working with the vaccinated animals. The strain that is used, is not a zoonosis. A risk assessment for biosecurity and occupational safety has been made and notified to the Directorate of Health and to the Norwegian Labour Inspection Authority. Import permission has been requested from the Norwegian Environment Agency. A notification to the Norwegian Food Authority (district office and border inspection control) has been made. The strain of our target bacterium is operating in sheep and other animals are refractory to this specific genotype, including humans. After immunization, a wild-type isolate will be used to evaluate the protective ability of the vaccine. The vaccine trial is based on a pilot study in which, twelve unexposed, 9-months-old lambs were vaccinated with a whole cell vaccine containing. This pilot study found immunological responses that needs improved approaches which are served by the current project.