Co‐administration of live attenuated Salmonella enterica serovar Typhimurium expressing swine interleukin‐18 and interferon‐α provides enhanced Th1‐biased protective immunity against inactivated vaccine of pseudorabies virus

Abstract

The co-administration of two or more cytokines may generate additive or synergistic effects for controlling infectious diseases. However, the practical use of cytokine combinations for the modulation of immune responses against inactivated vaccine has not been demonstrated in livestock yet, primarily due to protein stability, production, and costs associated with mass administration. In light of the current situation, we evaluated the immunomodulatory functions of the combined administration of swine interleukin-18 (swIL-18) and interferon-α (swIFN-α) against an inactivated PrV vaccine using attenuated Salmonella enterica serovar Typhimurium as a cytokine delivery system. Co-administration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α produced enhanced Th1-biased humoral and cellular immune responses against the inactivated PrV vaccine, when compared to single administration of S. enterica serovar Typhimurium expressing either swIL-18 or swIFN-α. Also, enhanced immune responses in co-administered piglets occurred rapidly after virulent PrV challenge, and piglets that received coadministration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α displayed a greater alleviation of clinical severity following the virulent PrV challenge, as determined by clinical scores and cumulative daily weight gain. Furthermore, this enhancement was confirmed by reduced nasal shedding of PrV following viral challenge. Therefore, these results suggest that oral co-administration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α provide enhanced Th1-biased immunity against inactivated PrV vaccine to alleviate clinical signs caused by PrV challenge.

Modulation of Humoral and Cell-Mediated Immunity Against Avian Influenza and Newcastle Disease Vaccines by Oral Administration ofSalmonella entericaSerovar Typhimurium Expressing Chicken Interleukin-18

“…Furthermore, recently it is reported that recombinant chIL-18 potentiated both the humoral and cell mediated immune responses against recombinant Newcastle disease virus vaccine (21,22) which directly supports our findings. The use of attenuated S. enterica serovar Typhimurium strain χ8501 as a successful mammalian and avian cytokine genes delivery system is well addressed at our laboratory in our several recent publications (13,17,23,24). According to our published data and other related published data, it is believed that the Salmonella bacteria used for cytokine delivery can persist in chickens for 3~7 weeks, depending on age of chickens, and can provide continuous long term protection against virus infection (12,25,26).…”

Synergistic effect of high‐mobility group box‐1 and lipopolysaccharide on cytokine induction in bovine peripheral blood mononuclear cells

“…Interferon‐γ plays an important role in both innate and adaptive immunity and also promotes Th1 polarization. The results of this study indicate that HMGB1 is a potent inducer of IFN‐γ expression and the heterocomplex comprising both HMGB1 and LPS synergistically up‐regulates the IFN‐γ expression.…”

Recombinant Salmonella enterica Serovar Typhimurium as a Vaccine Vector for HIV-1 Gag

“…Future studies should investigate this possibility of modulating the host immune system against HIV-1 Gag antigens by the production of in vivo functional cytokines by Salmonella vaccine vectors. Biologically-active cytokines can easily be co-delivered by Salmonella [118,119]. It has already been demonstrated that recombinant Salmonella co-expressing IL-2, IFN-γ, and macrophage migration inhibitory factor with recombinant antigen could afford to protect mice challenged with Leishmania major [120].…”