tetano
Editor, Senior Moderator
Sci Transl Med
. 2022 Mar 1;eabm0899.
doi: 10.1126/scitranslmed.abm0899. Online ahead of print.
Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models
Han-Yi Huang[SUP] #[/SUP][SUP] 1 2 [/SUP], Hsin-Yu Liao[SUP] #[/SUP][SUP] 1 [/SUP], Xiaorui Chen[SUP] #[/SUP][SUP] 1 [/SUP], Szu-Wen Wang[SUP] #[/SUP][SUP] 1 3 [/SUP], Cheng-Wei Cheng[SUP] 1 [/SUP], Md Shahed-Al-Mahmud[SUP] 1 [/SUP], Yo-Min Liu[SUP] 1 [/SUP], Arpita Mohapatra[SUP] 1 [/SUP], Ting-Hua Chen[SUP] 1 [/SUP], Jennifer M Lo[SUP] 1 [/SUP], Yi-Min Wu[SUP] 4 [/SUP], Hsiu-Hua Ma[SUP] 1 [/SUP], Yi-Hsuan Chang[SUP] 1 3 [/SUP], Ho-Yang Tsai[SUP] 1 3 [/SUP], Yu-Chi Chou[SUP] 5 [/SUP], Yi-Ping Hsueh[SUP] 6 [/SUP], Ching-Yen Tsai[SUP] 6 [/SUP], Pau-Yi Huang[SUP] 6 [/SUP], Sui-Yuan Chang[SUP] 7 8 [/SUP], Tai-Ling Chao[SUP] 7 [/SUP], Han-Chieh Kao[SUP] 7 [/SUP], Ya-Min Tsai[SUP] 7 [/SUP], Yen-Hui Chen[SUP] 9 [/SUP], Chung-Yi Wu[SUP] 1 [/SUP], Jia-Tsrong Jan[SUP] 1 [/SUP], Ting-Jen Rachel Cheng[SUP] 1 [/SUP], Kuo-I Lin[SUP] 1 [/SUP], Che Ma[SUP] 1 [/SUP], Chi-Huey Wong[SUP] 1 10 [/SUP]
Affiliations
Abstract
A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc-decorated state (S[SUB]MG[/SUB]) elicited stronger immune responses and better protection for human angiotensin converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from S[SUB]MG[/SUB] immunized mice that could neutralize wild type (WT) SARS-CoV-2 and VOCs with sub-picomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine.
. 2022 Mar 1;eabm0899.
doi: 10.1126/scitranslmed.abm0899. Online ahead of print.
Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models
Han-Yi Huang[SUP] #[/SUP][SUP] 1 2 [/SUP], Hsin-Yu Liao[SUP] #[/SUP][SUP] 1 [/SUP], Xiaorui Chen[SUP] #[/SUP][SUP] 1 [/SUP], Szu-Wen Wang[SUP] #[/SUP][SUP] 1 3 [/SUP], Cheng-Wei Cheng[SUP] 1 [/SUP], Md Shahed-Al-Mahmud[SUP] 1 [/SUP], Yo-Min Liu[SUP] 1 [/SUP], Arpita Mohapatra[SUP] 1 [/SUP], Ting-Hua Chen[SUP] 1 [/SUP], Jennifer M Lo[SUP] 1 [/SUP], Yi-Min Wu[SUP] 4 [/SUP], Hsiu-Hua Ma[SUP] 1 [/SUP], Yi-Hsuan Chang[SUP] 1 3 [/SUP], Ho-Yang Tsai[SUP] 1 3 [/SUP], Yu-Chi Chou[SUP] 5 [/SUP], Yi-Ping Hsueh[SUP] 6 [/SUP], Ching-Yen Tsai[SUP] 6 [/SUP], Pau-Yi Huang[SUP] 6 [/SUP], Sui-Yuan Chang[SUP] 7 8 [/SUP], Tai-Ling Chao[SUP] 7 [/SUP], Han-Chieh Kao[SUP] 7 [/SUP], Ya-Min Tsai[SUP] 7 [/SUP], Yen-Hui Chen[SUP] 9 [/SUP], Chung-Yi Wu[SUP] 1 [/SUP], Jia-Tsrong Jan[SUP] 1 [/SUP], Ting-Jen Rachel Cheng[SUP] 1 [/SUP], Kuo-I Lin[SUP] 1 [/SUP], Che Ma[SUP] 1 [/SUP], Chi-Huey Wong[SUP] 1 10 [/SUP]
Affiliations
- PMID: 35230146
- DOI: 10.1126/scitranslmed.abm0899
Abstract
A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc-decorated state (S[SUB]MG[/SUB]) elicited stronger immune responses and better protection for human angiotensin converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from S[SUB]MG[/SUB] immunized mice that could neutralize wild type (WT) SARS-CoV-2 and VOCs with sub-picomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine.