Oral administration of Salmonella enterica serovar Typhimurium expressing swine interleukin-18 induces Th1-biased protective immunity against inactivated vaccine of pseudorabies virus Seong Bum Kim a , Seon Ju Kim a , Byung Min Lee a , Young Woo Han a , Md Masudur Rahman a , Erdenebileg Uyangaa a , Jin Hyoung Kim b , Jin Young Choi a , Dong Jin Yoo c , Koanhoi Kim d , Seong Kug Eo a, * a College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea b Department of Biology, College of Natural Science, Chonbuk National University, Jeonju 561-756, Republic of Korea c Department of Hydrogen and Fuel Cells, Specialized Graduate School, Chonbuk National University, Jeonju 561-756, Republic of Korea d Department of Pharmacology, School of Medicine, Pusan National University, Busan 602-739, Republic of Korea 1. Introduction Pseudorabies virus (PrV) is an alpha herpesvirus of swine and is strongly related to the prototype alpha herpesvirus of human, herpes simplex virus type-1 (HSV- 1) (Van et al., 2011). PrV causes fatal swine disease known as Aujeszky’s disease that is characterized by neurological symptoms and death in young piglets, and respiratory and reproductive disorders in older pigs (Kluge et al., 1999; Hahn et al., 2010). Thus, the most significant economic losses of this disease are associated with the acute phase of the infection, in which there is a high abortion rate and neonatal mortality (Kluge et al., 1999; Hahn et al., 2010). Attempts to control PrV in swine and to reduce its associated economic losses have been classically made by active immunization with modified live or inactivated Veterinary Microbiology 155 (2012) 172–182 A R T I C L E I N F O Article history: Received 1 July 2011 Received in revised form 21 August 2011 Accepted 29 August 2011 Keywords: Attenuated Salmonella vaccine Swine interleukin-18 Th1-biased immunity Pseudorabies virus Inactivated vaccine A B S T R A C T Enhancing and/or modulating innate and adaptive immunity by cytokines appears to be greatly useful to provide effective protective immunity against infectious diseases. However, an effective delivery system for mass administration in livestock industry is needed because of limitations such as cost, labor, time, and protein stability. Here the immunomodulatory functions of swine interleukine-18 (swIL-18), known as IFN-g- inducing factor (IGIF), were evaluated in a vaccination model of pseudorabies virus (PrV) using attenuated Salmonella enterica serovar Typhimurium as the oral delivery system. The oral administration of S. enterica serovar Typhimurium expressing swIL-18 prior to vaccination with inactivated PrV vaccine induced enhanced levels of serum PrV-specific IgG and its IgG2 isotype, compared to administration of S. enterica serovar Typhimurium harboring the empty vector. Furthermore, S. enterica serovar Typhimurium expressing swIL-18 mounted Th1-biased cellular immune responses against PrV antigen, as evaluated by the production of IFN-g and IL-4 from peripheral blood mononuclear cells of piglets. Subsequently, Th1-biased immunity induced by S. enterica serovar Typhimurium expressing swIL-18 showed rapid response and rendered piglets displayed more alleviated clinical signs following the virulent PrV challenge. Also, this alleviation of clinical signs was further confirmed by the reduction of nasal excretion of PrV after challenge. The present study demonstrates the extended use of immunomodulatory functions of swIL-18 orally delivered by attenuated S. enterica serovar Typhimurium. ß 2011 Elsevier B.V. All rights reserved. * Corresponding author. Tel.: +82 63 270 3882; fax: +82 63 270 3780. E-mail address: vetvirus@chonbuk.ac.kr (S.K. Eo). Contents lists available at SciVerse ScienceDirect Veterinary Microbiology jou r nal h o mep ag e: w ww .els evier .co m/lo c ate/vetm ic 0378-1135/$ – see front matter ß 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.vetmic.2011.08.031