Inactivated poxviruses showed immunostimulating capacity. Such capacity is common to poxviruses of different genera . This fact renders poxviruses common vectors in vaccine development. On the other hand, poxviruses express a wide variety of proteins that are nonessential for virus replication in vitro but help the virus to evade the host response to infection that may in turn impair the immunological response against live viruses. Such nonstructural proteins includes soluble receptors for IFNα, β, TNFα, SOD-like protein,..etc. [16, 26, 35]. These facts together with the recurrence of SPPV infection among vaccinated flocks  let us to study first, the possible pivotal role of SPPV in inducing local immunosuppression as a crucial mechanism of immune escape, and second, to evaluate the potential beneficial systemic effect of SPPV on the host immune system.
Early immune response to SPPV at the site of inoculation provides an explanation for the ability of SPPV to induce local suppression at site of inoculation as indicated by increased IL-10 secretion and decreased SOD enzyme activity 12 h after injection. IL-10, a prototypic anti-inflammatory cytokine, that inhibits APC function and ultimately the induction of anti-virus immunity , prevents the differentiation of DC from monocytes , and inhibits the down regulation of receptor-mediated endocytosis and macropinocytosis following exposure to a soluble immunogen . In addition, IL-10 reduces the production of IL-2, IFN and TNF by murine Th1 cells  as well as the IL-12 production by APC . IL-10 may also, intervene at the level of antigen processing within the cell so that antigen is not degraded effectively and MHC class II molecules fail to load with peptide . Accordingly, enhanced secretion of IL-10 by SPPV has the capability to inhibit antigen presenting cell (APC) function as well as innate response and hence impairing the initiation of an acquired immune response. Such effect inhibits the generation of immunological memory necessary to immunity in subsequent exposure . Interestingly, both inactivated and attenuated SPPV showed significant increase in the IL-10 production from peritoneal macrophages. On the other hand, decreased in vitro SOD activity of cultured peritoneal macrophages noticed in SPPV treated groups may also enhance in vivo virus survival in, and in the presence of phagocytes. Superoxide is generated deliberately by phagocytes during the respiratory burst to kill microorganisms . The regulation of cellular SOD in poxvirus-infected cells might disrupt the balance of oxidants and antioxidants. Superoxide radicals arise during numerous oxidations in both living and nonliving systems and can act directly as oxidants or generate other reactive products that are toxic to cells, causing damage to lipid membranes, nucleic acid, carbohydrates, and proteins. SOD scavenges active oxygen species generated during aerobic metabolism. Consequently, aerobic existence is accompanied by a persistent state of oxidative siege, and the survival of a given cell is determined by its balance of reactive oxygen intermediates and antioxidants. Disturbance of this balance can lead to disease . Further, since oxidative stress can induce apoptosis , this may aid virus dissemination, a fact recorded with other poxviruses . Additionally, an increase in the cellular oxidant status results in activation of transcriptional factors, such as NF-κB , that may be necessary for replication of some viruses [27, 37]. Virulent viruses of SPPV may advocate similar immune evasion mechanisms that deflect down regulation and abortion of cell-mediated immunity.
In order to gain more insight into the processes underlying the possible immune stimulating effect of vaccination with SPPV, the ex-vivo levels of IL-12, SOD in splenic macrophages, and the magnitude of splenocyte proliferative response to PHA-P as well as the in-vivo effect of SPPV on humoral immune response to TD Ag; CRBC were studied. The obtained data showed that mice successfully vaccinated with SPPV displayed significant increases in IL-12 levels at 6 and 9 days post vaccination as compared to unvaccinated mice. IL-12 was examined at that time as it is likely that a minimum of five days is required to create an effective barrier by poxvirus-mediated T-cell activation and cytokine secretion . Interestingly, SOD, and lymphocyte blastogenesis as well as humoral immune response to CRBC were significantly enhanced in SPPV vaccinated mice especially in group treated with attenuated SPPV that may be related to virus replication. Enhanced splenic T-lymphocyte response to PHA-P in vaccinated mice indicates that SPPV may help in maintaining optimum T-cell responsiveness after vaccination. These effects might also rely on increased amounts of SPPV induced enhancement of IL-12 due to ability of IL-12 to induce early phase of NK and T cell activation . Using CRBC as model of TD Ag, it has been shown that SPPV was capable of enhancing TD Ab responses. Interestingly, enhancement was observed in mice vaccinated with either inactivated or attenuated SPPV. Furthermore, enhancement of lymphocyte blastogenesis and SOD were also recorded. These results are the first to demonstrate an immunostimulant effect of SPPV. Enhanced responses to TD Ags in SPPV vaccinated mice may be due to the enhancement of IL-12 production, increased responsiveness of T-lymphocyte and the SOD activity that were recorded in this study. IL-12 enhancement may initiate such cascade as it has been found to be the dominant factor in development of the Th1 phenotype and also directly, or from its associated release of type-1 cytokines, enhances the activation and production of Th1-associated immunoglobulins . In addition, IL-12 is not only a connective element between accessory cells and lymphocytes, but it is also a key molecule for programming the macrophage and dendritic cell functions . One of the major effects of IL-12 on macrophages and dendritic cells is the induction of IFN-γ, resulting in a positive feedback capable of activating them in different situations .
Our observations indicate that the SPPV-induced reduced macrophages' functions in a local event that occurs at the site of application 12 h after administration. In contrast, 3 till 12 days after injection of either inactivated or attenuated SPPV, enhanced functions of splenic macrophages and increased responsiveness of lymphocytes were found to be significantly increased that was more pronounced in attenuated vaccine rather than inactivated one. The combination of suppressive and stimulatory mechanisms is a complicated blend of viral survival strategy.