Mucosal Vaccines against HIV-1, Influenza, and Bioweapons

As much as 90% of infections occur at mucosal surfaces, yet the vast majority of effort is directed toward developing and testing vaccines that drive systemic and not mucosal responses. We believe mucosal vaccination will be particularly important for protection against HIV-1 and many bioweapons, since mucosal immune responses can provide a critical first line of defense at this key pathogen entry site. Given this, we are testing a variety of approaches to maximize antigen delivery to mucosal surfaces. In one approach, we have genetically re-engineered the potent adenovirus type 5 (Ad5) vector to display the mucosal-targeting sigma 1 protein of reovirus type 3 Dearing (T3D) (Mercier et al. PNAS 101(16): 6188-6193 2004). This chimeric virus targets both JAM-1 and sialic acid present on mucosal surfaces an on M cells in a species-independent fashion. We are currently testing the in vivo activity of this vector to enhance gene delivery to mucosal immune sites and decrease problematic gene and vector delivery to cells that do not promote immune response, but that produce dangerous side effects. We are testing Ad-sigma as a platform for the delivery of HIV-1, influenza, and biodefense antigens to couple with our existing genetic vaccine work. Other approaches include the development of oral capsule vaccines and testing of vectors that target dendritic cells.