Recent HIV vaccine designs attempting to elicit broadly neutralizing antibodies have not been completely effective and have not considered the potential role of mucus in blocking pathogen acquisition. Therefore, there is a need to explore alternative approaches to vaccine design. Our lab has recently shown that antibodies tightly bind mucus of the FRT. Due to the large amounts of antibodies at the mucosal surface we propose utilizing mucin-antibody interactions as a means of tethering HIV in the mucus which has the potential to block infection. Our lab has spearheaded a BMGF CAVD project identifying a high-affinity interaction between MUC16 and IgG from people chronically infected with HIV (HIV IgG). MUC16 is a mucin, originally discovered as CA125, that is found throughout the FRT. The specific goals of this training opportunity would be to develop a large-scale isolation protocol for these specialized antibodies with the goal of using them in a passive transfer assay. The Gallo Lab is a world leader in antibody production and macaque inmmunization. Seeing firsthand the quality control and the execution of these protocols would be an invaluable resource for my training as well as for the Hope lab. In addition the Gallo labs’ work with non-broadly neutralizing antibody assays would be an excellent training opportunity for characterizing these mucin-associated antibodies. One of the important questions proposed would be to understand if these passively transferred antibodies could localize to the FRT. Utilizing correlative spectroscopy we could transfer fluorescently tagged antibodies and measure their localization. Finally we would like to explore all of the potential novel effector functions of this new class of antibody. We will measure ADCC, FC binding, and trogocytosis. Success of this exchange will depend on the translation of these protocols in the Hope lab upon my arrival back in Chicago. In summary this exchange will help to determine if mucin-binding HIV specific antibodies could be used in a vaccine to block HIV infection by tethering the virus to mucus. This study could move the mucosal immunology field into a new direction of specific mucin-antibody interactions that have the potential of targeting pathogens to particular locations. MUC16 and HIV IgG may be first interaction to be characterized but the novel techniques and assays developed here will help lay the groundwork for future mucin-antibody research. This training opportunity will help guide my research from post-doctoral fellow to independent researcher. The insight gained from this project will usher in a new era of mucosal immunology with a therapeutic endgame being an efficient and effective HIV vaccine.
|Effective start/end date||11/1/14 → 3/1/15|
- Duke University (3836746//OPP1084285)
- Bill & Melinda Gates Foundation (3836746//OPP1084285)