Names: Alyssa Chen and Shriya Das

1. Names: Alyssa Chen and Shriya Das High Schools: Highland Park High School, Dallas TX and The Hockaday School, Dallas TX Mentor: Dr. Jinming Gao Project Title: Encapsulation of c-di-GMP Adjuvant into pH-Tunable Micelle-Based Nanoparticle Heightens Immune Response The bacterial second messenger, 3’, 5’-cyclic diguanylic acid (c-di-GMP), has recently been shown to stimulate innate immune response by activating a cytosolic signal transduction pathway. As such, c-di-GMP has the potential to be an adjuvant capable of eliciting protective immune responses against infections and cancer. However, the in vivo effect from c-di-GMP is limited, due to the inability of c-di-GMP to cross the plasma membrane to initiate the signal-transduction pathway found exclusively in the cytoplasm of cells. This project was designed to encapsulate c-di-GMP into an ultra-pH sensitive nanoparticle to facilitate the direct delivery of c-di-GMP into the cytoplasm of cells. Here we show that mouse dendritic cells stimulated with the c-di-GMP nanoparticle exhibited greatly enhanced expression of the immune co-stimulatory molecule CD86 and the MHC class-I molecule, more than that of cells stimulated with free c-di-GMP and that of cells stimulated with the nanoparticle alone. These results demonstrate that the c-di-GMP nanoparticle strongly stimulates innate immune responses, and suggest that the nanoparticle may be used as an adjuvant for future vaccine development.