Marek’s disease vaccine activates chicken macrophages

Authors: WANG, DAN - Shandong Agricultural University; SUN, SHUHANG - Shandong Agricultural University; HEIDARI, MOHAMMAD - US Department Of Agriculture (USDA)

Submitted to: Journal of Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2018
Publication Date: 5/31/2018
Citation: Wang, D., Sun, S., Heidari, M. 2018. Marek’s disease vaccine activates chicken macrophages. Journal of Veterinary Science. 19(3):375-383. https://doi.org/10.4142/jvs.2018.19.3.375.
DOI: https://doi.org/10.4142/jvs.2018.19.3.375

Interpretive Summary: Marek's disease virus (MDV), a highly cell-associated oncogenic alpha-herpes virus, is the etiological agent of Marek's disease (MD), a contagious lymphoproliferative disease of domestic chickens. Although MD vaccines have been in use for more than four decades, the specific mechanism of vaccine-induced protection is not clear. MD remains as a major economic threat to the poultry industry and consequently, elucidation of immune mechanisms of vaccine-mediated immunity is of critical importance. The purpose of the present study was to investigate the role of macrophages in CVI988/Ripens-mediated protection in two MD-susceptible and resistant chicken lines. Differential expression of macrophage-specific genes in the cecal tonsils, duodenum, and macrophages isolated from spleen of the vaccinated birds revealed activation of macrophages and a robust innate immune response to vaccination. Absence of an increase in the population of T cells in the tested tissues of the vaccinated birds at days 3 and 5 post-vaccination was suggestive of lack of an involvement of adaptive immune responses to the early stages of vaccination. Additionally, significant replication of the vaccine strain virus in the cecal tonsils and duodenum of the vaccinated susceptible line was detected by a Rispens-specific monoclonal antibody at day 5 post-vaccination. Moreover, the macrophage population was substantially increased in the duodenum of vaccinated susceptible and resistant chicken lines at the same time point when compared to the age and line-matched control birds. This study provides further insight into the role of the innate immune system in vaccine-induced protection and possible development of new recombinant vaccines with enhanced innate immune system activation properties.

Technical Abstract: To provide insights into the role of innate immune responses in vaccine-mediated protection, we investigated the effect of Marek’s disease (MD) vaccine, CVI988/Rispens, on the expression patterns of selected genes associated with activation of macrophages in MD-resistant and MD-susceptible chicken lines. Upregulation of interferon gamma, interleukin (IL)-1beta, IL-8, and IL-12 at different days post-inoculation (dpi) revealed activation of macrophages in both chicken lines. A strong immune response was induced in cecal tonsils of the susceptible line at 5 dpi. The highest transcriptional activities were observed in spleen tissues of the resistant line at 3 dpi. No increase in the population of CD3+ T cells was observed in duodenum of vaccinated birds at 5 dpi indicating a lack of involvement of the adaptive immune system in the transcriptional profiling of the tested genes. There was, however, an increase in the number of macrophages in the duodenum of vaccinated birds. The CVI988/Rispens antigen was detected in the duodenum and cecal tonsils of the susceptible line at 5 dpi but not in the resistant line. This study sheds light on the role of macrophages in vaccine-mediated protection against MD and on the possible development of new recombinant vaccines with enhanced innate immune system activation properties. Keywords: CVI988/Rispens, Marek’s disease, cecal tonsils, duodenum, macrophages