Technical Abstract: Eimeria is a protozoan parasite which causes coccidiosis, a major parasitic disease of poultry that is indigenous to most regions of the world and causes intestinal damage with reduced body weight gain. Conventional disease control methods have relied on prophylactic chemotherapy, but alternative methods are needed due to increasing governmental restrictions on the use of drugs in animal production and high costs of new drug development. Vaccination with live or attenuated parasites is a practical alternative to drugs for coccidiosis control but vaccination is limited by the lack of cross-protection against Eimeria species absent in the vaccine formulation and the emergence of novel antigenic variants. In this paper, ARS scientists collaborated with scientists at the University of Zaragusa in Spain in series of studies to develop a second-generation coccidiosis vaccine that cross-protect against multiple coccidia species. As part of this systematic approach, they have recently developed a new method to isolate and identify intestinal dendritic cells which are involved in processing parasite antigens to initiate immune response following Eimeria infection. The results showed that dendritic cells from chicken gut can effectively communicate with intestinal lymphocytes to elicit antigen-specific immune response against coccidiosis. This new information will facilitate the development of recombinant vaccines against poultry coccidiosis and will be used by poultry industry scientists.