Abstract Book 2010 - CIMT Annual Meeting

014 Abbas | Therapeutic vaccination
Vaccine development through antigen targeting to mannose
receptor
Zaigham Abbas 1 , Richard Pleass 2 , Giuseppe Mantovani 3 , Lindy Durrant 1 and Luisa Martinez-Pomares 1
1 School of Molecular Medical Sciences, University of Nottingham
2 School of Biology, University of Nottingham
3 School of Pharmacy, University of Nottingham
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Dendritic cells (DC) are unique antigen presenting
cells which play a major role on the antigen presentation
and initiation of the immune response
by regulating B- and T- cell activation. Antigen
targeting to DC receptors is an effective, safe and
specific method for the vaccine development. MR
is an endocytic receptor expressed by subpopulations
of DC. Antigen targeting through MR leads
to enhanced antigen uptake and presentation to T
cells which makes it a favourite receptor for the development
of vaccines against diseases that require
T-cell immunity such cancer and viral infections.
We have used two approaches to target antigen to
MR; (i) MR-specific chimeric antibodies carrying
several model antigens and (ii) antigens conjugated
to novel glycopolymers. The binding efficiency of
the chimeric antibodies has been assessed by using
ELISA and BIACORE and the glycopolymers have
been tested for their interaction with MR. These
glycopolymers will be coupled to a mutated form
of the model antigen ovalbumin (OVA) lacking Nglycosylation
sites as native OVA is an excellent MR
ligand. These novel reagents are currently being
tested for their ability to induce T-cell activation
in vitro using co-cultures of antigen presenting
cells and T cells and in-vivo. Our results will
greatly benefit the development of antigen delivery
methods suitable for robust T cell activation.