BIO Asia–Taiwan 2021 亞洲生技大會

BIO Asia–Taiwan 2021 亞洲生技大會

講師

Alex Ma

Session 6 – Pandemic Control after Vaccination (B)

Date: 22 July (Thursday)
Time: 10:40 – 12:10 (GMT+8)

Alex Ma

Professor
Genomics Research Center
Academia Sinica

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.
 

Speech title & Synopsis

Broad-Spectrum Vaccine Against SARS-CoV-2 and Variants

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.