|Del Cacho, Emilio|
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2012
Publication Date: 6/6/2012
Citation: Del Cacho, E., Gallego, M., Lee, S.H., Lillehoj, H.S., Quilez, J., Lillehoj, E., Sanchez-Acedo, C. 2012. Induction of protective immunity against Eimeria tenella, Eimeria maxima, and Eimeria acervulina infections using DC-derived exosomes. Infection and Immunity. 80:1909-1916. Interpretive Summary: For many disease such as coccidiosis which is a complex intestinal disease that is of major economic importance in chickens, an alternative strategy to reduce the use of antibiotics will be necessary. However, lack of information on immunogenic parasite proteins limits the progress with the developing recombinant vaccines. In this study, ARS scientists collaborated with scientists at the University of Zaragoza in Spain to develop a novel strategy to identify immunogenic proteins of coccidia parasites as a potential vaccine against coccidiosis. This novel approach to vaccination against coccidiosis is to exploit dendritic cells (DCs) as first step in the development of a second-generation coccidiosis vaccine. DCs are immunologic sentinels that induce effective antigen-specific immune responses. The major findings of this report give evidence that exosomes released by DCs incubated with parasite antigens stimulated a robust local T-cell response and conferred protection against the live parasites. The present study is a promising approach for the achievement of a multivalent vaccine that includes antigens from a variety of species in order to overcome one of the major problems associated with the development of an anticoccidial vaccine, the immunological diversity among the Eimeria species. These results will benefit poultry animal health industry to develop a recombinant vaccine against avian coccidiosis using non-viable, parasite antigens.
Technical Abstract: This study describes a novel immunization strategy against avian coccidiosis using exosomes derived from Eimeria parasite antigen (Ag)-loaded dendritic cells (DCs) in the absence of soluble Ag. Chicken intestinal DCs were isolated and pulsed in vitro with a mixture of sporozoite-extracted Ags from E. tenella, E. maxima, and E. acervulina and the cell-derived exosomes were isolated. Chickens were non-immunized or immunized intramuscularly with Ag-pulsed DC exosomes and subsequently non-infected or coinfected with E. tenella, E. maxima, and E. acervulina oocysts. Immune parameters compared amongst the non-immunized/non-infected, non-immunized/infected, and immunized/infected groups were the numbers of cells secreting Th1 cytokines, Th2 cytokines, and Ag-reactive antibodies in vitro, and in vivo readouts of protective immunity against Eimeria challenge infection. Intestinal cecal tonsils and Peyer’s patches and spleens of immunized and infected chickens had increased numbers of cells secreting the Th1 cytokines IL-2-, IL-16-, and IFN-', greater Ag-stimulated proliferative responses, and higher numbers of Ag-reactive IgG- and IgA-producing cells following in vitro stimulation with E. tenella, E. maxima, or E. acervulina sporozoite Ags, compared with the non-immunized/non-infected and non-immunized/infected controls. By contrast, the numbers of cells secreting the Th2 cytokines IL-4 and IL-10 were diminished in immunized and infected chickens compared with the non-immunized/non-infected and the non-immunized/infected controls. Chicken immunized with Eimeria Ag-loaded DC exosomes and infected in vivo with Eimeria oocysts had increased body weight gains, reduced feed conversion ratios, diminished fecal oocyst shedding, lessened intestinal lesion scores, and reduced mortality compared with the non-immunized/infected controls. These results suggest that successful field vaccination may be possible again st avian coccidiosis using non-viable, parasite Ag-pulsed, DC-derived exosomes.