Elimination of
Antibody-Encoded Tolerogenic Signals for Development of an Improved
Dendritic Cell-Targeted Vaccine Delivery Platform
The highly specific capacity of
antibodies for targeting dendritic cell (DC) endocytic receptors can be
harnessed for efficient vaccine antigen delivery to the
antigen-presenting pathway. To improve DC-targeted vaccination, we
set out to eliminate tolerogenic sequences in the well-studied DC
targeting antibody,
αDEC205, to produce a
vaccine delivery platform that will independent of additional
non-specific immune-stimulators. This goal is based on our recent
discovery of a set of natural regulatory T-cell epitopes derived from
human immunoglobulins that induce tolerance by stimulation of regulatory
T cells. This project will involve production of sequence modified
antibodies and testing for reduced tolerogenicity in animal models and
human peripheral blood cell cultures.
Please note that this project will take
place on URI's Providence Campus and also involves the use of vertebrate
animals.