Ad5-vectored FMDV vaccine elicits antigen-specific CTL responses in swine. (43.10)

Abstract

Abstract Foot-and-mouth disease virus (FMDV) is a highly infectious picornavirus that causes disease in cloven-hoofed animals. Neutralizing antibodies are thought to play a primary role in FMDV immunity, and their induction forms the basis for current vaccine approaches. However, the role of cytotoxic T-lymphocytes (CTLs) in recovery and protection has remained largely unexplored. Immune evasion strategies of FMDV are predicted to impair the development of functional CTL assays. Specifically, virus encoded proteases inhibit expression of Class I MHC molecules by infected cells. In order to overcome these difficulties, we have analyzed the response to a recombinant, human Adenovirus 5 (huAd5) vectored, FMDV vaccine. Swine homozygous for MHC were vaccinated with a replication-defective huAd5 expressing the unprocessed capsid polyprotein of FMDV, strain A24. An MHC-matched cell line was used for antigen stimulation and as a source of target cells in cellular cytotoxicity assays. PBMCs from vaccinated animals were incubated with Ad5-infected target cells for 3-5 days. CD6+ T cells were isolated and mixed with Ad5-FMDV infected target cells. Antigen-specific killing was detected relative to control target cells. This suggests that vaccination with adenovirus vectored vaccine constructs can induce a functional CTL response against epitopes of FMDV in a MHC restricted manner.