Location: Animal Disease Research Unit
Project Number: 2090-32000-043-008-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Aug 1, 2025
End Date: Jul 31, 2028
Objective:
This work will generate information and tools required to develop methods bovine anaplasmosis, a tick-borne disease of cattle that costs US cattle producers $300 million per year and is found in every state. Bovine anaplasmosis is caused by Anaplasma marginale. This bacterium is an obligate intracellular pathogen. Thus, to cause disease and be transmitted by ticks, A. marginale must enter and replicate in cattle and tick cells. This work will advance efforts to prevent host cell entry and thus prevent disease and transmission.
The specific goal of the work proposed in this agreement is to determine: 1) the amount of variation the A. marginale proteins required for entry into cattle and tick cells; and 2) the amount of variation in the tick and cow receptors on cells that interact with those A. marginale proteins. The third goal of this work is to develop antibodies for immune depletion studies in cattle. This will allow us to identify the immune responses and cells required for protective immunity to bovine anaplasmosis which is foundational for vaccine development.
Approach:
The A. marginale genes that encode the proteins required for host cell entry will be sequenced from A. marginale-infected cattle throughout the US. Similarly, the genes encoding the cognate receptors will be sequenced from tick vectors and US cattle populations. To produce antibodies, the cDNA from the existing mouse monoclonal antibodies will be cloned and sequenced. The constant regions from the mouse monoclonal antibodies will be replaced by constant regions from bovine antibodies. Studies will then be done in cattle to determine if the targeted immune cells can be depleted with the monoclonal antibodies.