NKp46+CD3+ cells as a Novel Target for Vaccines Against Bovine TB

The Morrison and Vordermeier laboratories have recently identified a novel NKp46+CD3+ non-conventional T-cell population in cattle and demonstrated that a subset of these cells recognise phosphatidylinositol mannosides (PIMs - a group of membrane bound lipids) from Mb. In this project we propose to i) examine NKp46+CD3+ T-cell responses during a BCG-immunisation/Mb-challenge study so as to gain some insights into the role of lipid-specific T-cells in bTB and ii) explore the breadth of lipids from TB that act as antigens for bovine T-cells and evaluate their potential as vaccine antigens. Specifically we aim to address the following questions: 1. What are the quantitative and kinetic characteristics of the NKp46+CD3+ T-cell response following BCG vaccination and subsequent exposure to M. bovis? 2. What are the functions of NKp46+CD3+ T-cells recognising mycobacteria? 3. Which mycobacterial lipids are recognised by NKp46+CD3+ (and other) bovine T-cells? 4. Can vaccination with mycobacterial lipid extracts elicit NKp46+CD3+ T-cell responses in vivo? The combined results of the proposed studies will provide the fundamental basic immunological data to determine if inclusion of lipid antigens has the potential to enhance the immunogenicity and protective efficacy of new bTB vaccines. We also will perform analyses to define if lipid antigens could be used as novel DIVA reagents.

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