Advancing the analysis of bovine class I MHC restricted T cell responses to vaccination

Project summary

The classical viral vaccine approaches using inactivated virus or live-attenuated virus have been the core of vaccination efforts against many economically important diseases of food animals. Although these efforts have yielded much success, challenges remain, including little cross-serotype protection against genetically diverse pathogens and inadequate duration of immunity.

Commonly, viral infections are characterized by induction of cytotoxic T lymphocytes (CTL), but only live, attenuated virus vaccines stimulate this critical component of immunity. We aimed to develop an assay for detection of CTL specific for foot-and-mouth disease virus (FMDV) and assess if modified adenovirus-vectored FMDV vaccine could induce CTL activity in cattle and further expand these technologies to other livestock such as sheep and goats.

The replication defective adenovirus-vectored vaccine platforms carry advantages of both classical types of inactivated virus vaccines in being safe, but like attenuated vaccines, express viral antigens inside infected cells so that class I major histocompatibility complex (MHC) restricted antigen presentation can occur efficiently. As CTL assays require matching of these transplantation antigen genes, we first aimed to develop a bank of class I MHC typed fibroblast cell lines for subsequent use as “matching” cell lines for the target cell in the CTL killing assays by cells from MHC matched animals used in the vaccine trial.

To develop these cell lines, we hypothesised that diversity of class I MHC in Holstein Friesian cattle is very low and that we require only a few typed fibroblast cell lines to match most of the animals in the vaccine trial. Consequently, we successfully isolated and cryopreserved fibroblast cell lines from Holstein Friesian cattle skin. MHC typing was carried out on these cell lines using assays the visiting scientist applied in his home region analysing the MHC diversity of indigenous cattle breeds of Zambia. The cell lines we isolated are now ready to be used as MHC compatible target cells for assays measuring CTL responses in vaccine trials.