Date: 22 July (Thursday)
Time: 10:40 – 12:10 (GMT+8)
Genomics Research Center
Dr. Ma received his B.S. (1992) from National Taiwan University, and M.S. (1996) and Ph.D. (2000) degrees in Chemistry from University of Pennsylvania, and was a postdoc fellow at University of California, San Diego and the Scripps Research Institute (2001-2004). Dr. Ma is a recipient of the Skaggs Postdoctoral Fellowship (2001), the TWAS Young Affiliate (2009-2013), Academia Sinica Significant Research Achievements (2009), the Academia Sinica Award for Junior Research Investigators (2010), the Young Scholar Award of Tien-De Li Biomedical Foundation (2011), Academia Sinica Career Development Award (2013), Exceptional Merit in Academic Award Taiwan Rotary Foundation (2014) and Taiwan Bio-Development Foundation endowed Chair in Biotechnology (2014). His expertise is in structural biology of membrane proteins and glycoproteins. Recent research interests cover new antibiotics against drug-resistant bacterial infections, universal influenza vaccines, and drug discovery in infectious diseases and cancers.
A major challenge to end the pandemic caused by SARS-CoV-2 and emerging variants is to develop broadly protective vaccines with long-term immunity. The viral surface spike (S) protein has been the major immunogen for vaccine development; however, it is frequently mutated and heavily glycosylated to evade host immune response, and the highly conserved epitopes are largely shielded by glycans. Here we show that S protein glycosylation is cell specific, with differential effect on viral infectivity, and the major glycoforms from lung epithelial cells, the primary cells for infection, are mainly complex-type and require sialylation for efficient infection. Immunization of S protein with all N-glycans trimmed to the monoglycosylated state (Smg) elicits stronger neutralizing antibody and balanced Th1/Th2 responses toward the wild type and the variants of concern, and is significantly more protective for hACE2 transgenic mice challenged with a lethal dose of virus as compared to the fully glycosylated S protein (Sfg). A monoclonal antibody identified from the single B cell clones of Smg immunized mice is also able to neutralize the wild type and the variants, demonstrating that removal of glycans from S protein to better expose the highly conserved sequences is an effective approach to universal vaccine development.