Advances in immunology, biochemistry, and biology have enabled scientists to rapidly identify the sequences and structures of antigens, the substances in vaccines that stimulate immune responses against disease. For an antigen to be valuable as a vaccine, however, scientists must find a way of giving it to individuals so that it predictably results in the desired immune response. Currently, scientists face roadblocks in producing vaccines that predictably raise protective immune responses against several diseases, notably HIV and malaria.

Dr. Steinman’s team is developing vaccines that stimulate the immune system’s dendritic cells, which are known to play an important role in stimulating protection against infectious diseases.  One approach is to engineer vaccine antigens into monoclonal antibodies against receptors on the surface of dendritic cells. A secondary approach involves engineering genes for the antigens of interest into the yellow fever virus.  The project will focus on creating experimental vaccines for a range of diseases, including HIV and malaria. If successful, this technology could identify a better way to create vaccines that stimulate multiple components of the body’s immune response, including those that have been difficult to target with existing vaccine approaches.

The project team plans to engineer protein antigens into monoclonal antibodies that recognize endocyctic receptors on dendritic cells, selectively and efficiently targeting vaccine proteins to the dendritic cells in lymphoid tissues. They have chosen DEC-205 as the targeted dendritic cell receptor. The team expects to proceed through Phase I safety and immunogenicity testing of an HIV/AIDS vaccine. Their studies of this vaccine strategy for other diseases, including malaria and Epstein-Barr virus, will focus on proof-of-concept in mouse models of infection.