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Title:   Author  item
                                            Kim, Duk Kyungitem
                                            Lillehoj, Hyunitem
                                            Lee, Sungitem
                                            DOMINOWSKI, PAUL - Pfizer, Incitem
                                            YANCEY, ROBERT - Pfizer, Incitem
                                            LILLEHOJ, ERIK - University Of Maryland
  Submitted to: Avian Diseases
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 12/1/2011
                                    Publication  Date: 1/5/2012
                                    Citation: Kim, D., Lillehoj, H.S., Lee, S.H., Dominowski, P., Yancey, R., Lillehoj, E. 2012. Effects of novel vaccine/adjuvant complexes on the protective immunity against Eimeria acervulina and transcriptome profiles. Avian Diseases. 56:97-109.Interpretive Summary: Although many commercial vaccines in poultry use live or attenuated pathogens, there is a timely need for improved vaccine formulation to effectively control infectious diseases of poultry in the future. One of the novel ways of increasing the effectiveness of vaccines is to increase the immunogenicity of proteins using adjuvants which are known to potentiate immunogenic potential of weak protein antigens. In order to investigate the effect of novel adjuvant formulation in poultry vaccination, ARS scientists collaborated with scientists from Pfizer Animal Health to formulate effective combinations of recombinant parasite antigen and novel adjuvant mixtures (designated as QCDC and QCDCR) to modulate host protective immunity in poultry. To validate the role of these new immunomodulatory formulations, ARS scientists investigated host gene expression profiles of the intestinal samples from chickens given an experimental avian coccidiosis. The results showed that QCDCR adjuvant-vaccine formulation significantly enhanced protective immunity against coccidiosis compared to QCDC mixture. Furthermore, many genes associated with innate immune response were significantly changed in chickens treated with QCDCR indicating significant immunomodulatory function of this unique adjuvant formulation.  These new findings will help industry to formulate more effective vaccines for poultry to reduce economic losses due to infectious diseases.
                                Technical Abstract: This study investigated the ability of two novel adjuvant formulations, QCDC (Quil A/cholesterol/DDA/Carbopol) and QCDCR (QCDC/Bay R1005), in combination with a recombinant profilin vaccine, to modulate host protective immunity and to alter gene expression during experimental avian coccidiosis.  Vaccination with profilin plus QCDCR significantly reduced the severity of intestinal lesions and increased mitogen-induced lymphocyte proliferation in infected chickens compared with immunization with profilin alone or profilin plus QCDC.  Immunization with profilin plus QCDC or profilin plus QCDCR increased body weight gain but had no effect on fecal oocyst shedding of chickens infected with Eimeria acervulina compared with birds vaccinated with profilin alone.   The results of global gene expression analysis revealed that compared with PBS controls, (a) chickens vaccinated with profilin alone had 71 up-regulated and 56 down-regulated mRNA transcripts, (b) chickens immunized with profilin plus QCDC had 198 up-regulated and 247 down-regulated mRNAs and (c) birds immunized with profilin plus QCDCR had 210 up-regulated and 267 down-regulated mRNAs.  Compared with birds vaccinated with profilin alone, (a) chickens given profilin plus QCDC had 60 up-regulated and 104 down-regulated transcripts and (b) chickens immunized with profilin plus QCDCR had 103 up-regulated and 130 down-regulated mRNAs.  Finally, chickens vaccinated with profilin plus QCDCR had 193 up-regulated and 204 down-regulated transcripts compared with birds given profilin plus QCDC.  Biological function and network analysis revealed that the majority of altered transcripts were encoded by immune-related genes.


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