Targeting of caveospheres to human immune cells

Project Summary

We have made exciting advances on the ability to attach antibodies to caveospheres to target these vaccine particles to immune cells. This joint effort across a team of three CBNS Chief Investigators (Parton, Johnston, and Kent) bringing complementary skills to the problem illustrates the power of the CBNS to tackle large problems.

Attaching antibodies to caveospheres was achieved through the expression of a “z-domain” of staphylococcal Protein A, which then binds the Fc portion of antibodies. This allowed us to test multiple different targeting antibodies with the same particle. We have shown that we could target either B cell or T cells (types of immune cells) both in cells in tissue culture but also in the complex environment of human blood. By targeting another molecule on T cells (the CCR5 receptor) we were able to show that particles can be internalised into T cells.

The CCR5 receptor is critical in the entry of HIV into cells, meaning that we have a platform to target our particles to the same target cells as HIV. This opens up exciting possibilities in the delivery of novel anti-HIV therapeutics, as well as driving the development of novel vaccines.