Published: 05 May 2017 | Last Updated: 05 May 2017 15:02:18

Professor Dirk Werling and Dr Denis Larkin have recently been awarded a BBSRC grant, together with Prof Kurt Drickamer and Dr Maureen Taylor (both Imperial College London).

The innate immune system is the first line of defence against invading pathogens. Cells of the innate immune system, such as macrophages and dendritic cells express a variety of receptors that bind to sugar (glycan) targets. These receptors, known as lectins, perform a dual function: under non-infectious conditions, they support the normal function of the immune system through enhancing the interaction of macrophages/dendritic cells with T cells. Under infectious conditions, they aide the recognition of pathogens that express specific glycan motifs in case of an infection. Distinguishing host cells from pathogens by these receptors derives from their ability to bind pathogen-specific surface sugars.

Recently, the idea of using glycan structures as vaccine adjuvants/vaccine delivery systems to target specific innate immune cell subsets through the sugar-binding receptors has been explored. Using this approach robust humoral and cellular immune responses have been induced in mice. Thus, in addition to providing an understanding of innate immune cell - T cell interaction in farm animals in more detail, the proposed work will provide a basis for exploiting adjuvant-like properties of glycans themselves resulting from their ability to activate both inflammatory and phagocytic receptors expressed on antigen-presenting cells. Our preliminary data demonstrate that there are substantial differences between the glycan-receptors expressed in different mammalian species, and the ligands that they recognise. This observation has important implications for vaccine design for farm animals, specifically ruminants as studied here, as it means that vaccine adjuvants designed and tested in the human and/or murine system may not work in other mammalian species, a fact supported by the recent failure of mycobacterial vaccines in the appropriate host.  

In a newly funded £1,1M BBSRC grant, the team aims to identify the glycan (lectin) receptors in the bovine genome and to understand their function. This may provide new avenues to understand the first steps in host pathogen interaction. As the key way of reducing antibiotic dependence, and thus the reduction of AMR is to improve current vaccine strategies, the gained knowledge may also provide the basis for the development of more host-specific adjuvant/vaccine-delivery systems.

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