Vaccines are one of the greatest achievements of biomedical science. While most vaccines are injected, there is a growing interest in developing and improving vaccines that can be inhaled. The delivery of vaccine directly to the mucosal surfaces that line the nose and lungs is a more effective way to produce immunity against respiratory pathogens such as pneumococcus and influenza. As these mucosal vaccines are relatively cheap and easy to apply, they would also be suitable for use in developing countries and during emergencies. Currently, there is no approved mucosal vaccine adjuvant in U.S. Developing safe and effective mucosal vaccine adjuvants which help to boost targeted immune response is key to the development of mucosal vaccines.
Cyclic dinucleotides (CDNs) are promising mucosal vaccine adjuvant candidates. They elicit potent and balanced humoral and cellular immune response protecting animals from viral and bacterial infection. CDNs include cyclic di-AMP (CDA), cyclic di-GMP (CDG) and the newly discovered 2’5’-3’5’-cyclic GMP-AMP (2’3’-cGAMP). STING (stimulator of interferon genes) is the mammalian receptor for CDNs. We first showed that the mucosal adjuvant CDNs enhance antigen uptake and processing in animals and directly activates dendritic cells (DC) in vivo. We further showed that STING-dependent TNFα production is critical for the mucosal adjuvant activity of CDNs in vivo.
Our primary goal is to 1) decipher the in vivo cellular and molecular mechanism of action of CDN; 2) advance CDN as safe and efficacious mucosal vaccine adjuvants in human. Our approaches include knockout, knockin, conditional knockout, and conditional WT mice. We are also endeavoring to expand our research into human samples.
Other research interests in the lab include 1) Understanding the effects of common human STING variations on licensed pneumococcal vaccines Pneumovax®23 and Prevnar13® effectiveness in vivo; 2) Understanding the role of STING in host defense against pneumococcal infections in vivo.
Current Research Projects/Grants
Completed Research Projects/Grants