Progress and obstacles in vaccine development for the ehrlichioses

Ehrlichia are tick-borne obligately intracellular bacteria that cause significant diseases in veterinary natural hosts, including livestock and companion animals, and are now considered important zoonotic pathogens in humans. Vaccines are needed for these veterinary and zoonotic human pathogens, but many obstacles exist that have impeded their development. These obstacles include understanding genetic and antigenic variability, influence of the host on the pathogen phenotype and immunogenicity, identification of the ehrlichial antigens that stimulate protective immunity and those that elicit immunopathology, development of animal models that faithfully reflect the immune responses of the hosts and understanding molecular host-pathogen interactions involved in immune evasion or that may be blocked by the host immune response. We review the obstacles and progress in addressing barriers associated with vaccine development to protect livestock, companion animals and humans against these host defense-evasive and cell function-manipulative, vector-transmitted pathogens.