Anaplasmosis: focusing on host-vector-pathogen interactions for vaccine development.

Anaplasma marginale and A. phagocytophylum are intracellular rickettsiae that cause bovine anaplasmosis and human granulocytic anaplasmosis, respectively. The ultimate vaccine for the control of anaplasmosis would be one that reduces infection and transmission of the pathogen by ticks. Effective vaccines for control of anaplasmosis are not available despite attempts using different approaches, such as attenuated strains, infected erythrocyte and tick cell-derived purified antigens, and recombinant pathogen and tick-derived proteins. Three lines of functional analyses were conducted by our laboratory to characterize host-tick-Anaplasma interactions to discover potential vaccine candidate antigens to control tick infestations and the infection and transmission of Anaplasma spp.: (1) characterization of A. marginale adhesins involved in infection and transmission of the pathogen, (2) global expression analysis of genes differentially expressed in HL-60 human promyelocytic cells in response to infection with A. phagocytophilum, and (3) identification and characterization of tick-protective antigens by expression library immunization (ELI) and analysis of expressed sequence tags (EST) in a mouse model of tick infestations and by RNA interference in ticks. These experiments have resulted in the characterization of the A. marginale MSP1a as an adhesin for bovine erythrocytes and tick cells, providing support for its use as candidate vaccine antigen for the control of bovine . Microarray analysis of genes differentially expressed in human cells infected with A. phagocytophilum identified key molecules involved in pathogen infection and multiplication. The screening for tick-protective antigens resulted in vaccine candidates reducing tick infestation, molting, and oviposition and affecting Anaplasma infection levels in ticks.