Lei Jin, PhD, MSC
Assistant Professor of Medicine
Biological Scientist 2
Seema Ben Patel
Graduate PhD Student
Biological Scientist 2
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
- NIH-5R01AI110606: Mechanisms of STING-Mediated Mucosal Vaccine Adjuvant Activity of Cyclic di-GMP – 2014 ~2019
- NIH-1R21AI125999: Impact of Human STING Variants on Pneumococcal Vaccine Effectiveness – 2016~2018
- R21AI132865: Mechanisms of STING-dependent IFNgamma production during pulmonary pneumococcal infection– June 2018 – May 2020
Completed Research Projects/Grants
- NIH-R56AI110606: Mechanisms of STING-Mediated Mucosal Vaccine Adjuvant Activity of Cyclic di-GMP – July 2014 ~ Nov 2014
- NIH-R21AI099346 (Subcontract): Mouse Modeling of a Human STING Gene Variant for Infectious Disease – 2012 ~ 2015
- Jin L, Waterman PM, Jonscher KR, Short CM, Reisdorph NA, Cambier JC. MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals. Mol Cell Biol. 2008 Aug;28(16):5014-26.
- Jin L, Xu LG, Yang IV, Davidson EJ, Schwartz DA, Wurfel MM, Cambier JC. Identification and characterization of a loss-of-function human MPYS variant. Genes Immun. 2011 Jun;12(4):263-9
- Jin L, Hill KK, Filak H, Mogan J, Knowles H, Zhang B, Perraud AL, Cambier JC, Lenz LL MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J Immunol. 2011 Sep 1;187(5):2595-601
- Blaauboer SM, Gabrielle VD, Jin L MPYS/STING-mediated TNF-alpha, not type I IFN, is essential for the mucosal adjuvant activity of (3′-5′)-cyclic-di-guanosine-monophosphate in vivo. J Immunol. 2014 Jan 1;192(1):492-502
- Blaauboer SM, Mansouri S, Tucker HR, Wang HL, Gabrielle VD, Jin L The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo. Elife. 2015 Apr 21;4.
- Patel, S., Blaauboer, S.M., Tucker, H.R., Mansouri, S., Ruiz-Moreno, J.S., Hamann, L., Schumann, R.R., Opitz, B., Jin, L. The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele. J Immunol. 198(2):776-787, 2017 (Highlighted In This Issue, top 10% of the articles published in the Journal).
- Complete List of Publications
- Mansouri, S, Patel, S, Blaauboer, S.M, Wang, W, Katikaneni, D. S, Schattgen, S, Fitzgerald, K and Jin, L. 2018. Immature lung TNFR2– cDC2 subpopulation activates moDCs to promote cyclic di-GMP mucosal adjuvant responses in vivo. Mucosal Immunology, epub Oct 16, 2018.