PMID- 35230146
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20230110
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 14
IP  - 639
DP  - 2022 Apr 6
TI  - Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced 
      protective responses in animal models.
PG  - eabm0899
LID - 10.1126/scitranslmed.abm0899 [doi]
LID - eabm0899
AB  - 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(MG)) 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(MG)-immunized mice that could 
      neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar 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.
FAU - Huang, Han-Yi
AU  - Huang HY
AUID- ORCID: 0000-0002-6824-6993
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
AD  - GIP-TRIAD Master's Program in Agro-Biomedical Science, National Taiwan University 
      College of Medicine, Taipei 100233, Taiwan.
FAU - Liao, Hsin-Yu
AU  - Liao HY
AUID- ORCID: 0000-0002-7105-612X
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Chen, Xiaorui
AU  - Chen X
AUID- ORCID: 0000-0002-4492-0883
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Wang, Szu-Wen
AU  - Wang SW
AUID- ORCID: 0000-0002-1240-6126
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
AD  - Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, 
      Taiwan.
FAU - Cheng, Cheng-Wei
AU  - Cheng CW
AUID- ORCID: 0000-0003-3491-8920
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Shahed-Al-Mahmud, Md
AU  - Shahed-Al-Mahmud M
AUID- ORCID: 0000-0002-4285-7016
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Liu, Yo-Min
AU  - Liu YM
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Mohapatra, Arpita
AU  - Mohapatra A
AUID- ORCID: 0000-0003-3468-6912
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Chen, Ting-Hua
AU  - Chen TH
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Lo, Jennifer M
AU  - Lo JM
AUID- ORCID: 0000-0002-3002-9491
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Wu, Yi-Min
AU  - Wu YM
AUID- ORCID: 0000-0001-9745-6298
AD  - Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
FAU - Ma, Hsiu-Hua
AU  - Ma HH
AUID- ORCID: 0000-0003-0073-6985
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Chang, Yi-Hsuan
AU  - Chang YH
AUID- ORCID: 0000-0002-8643-9959
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
AD  - Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, 
      Taiwan.
FAU - Tsai, Ho-Yang
AU  - Tsai HY
AUID- ORCID: 0000-0002-7666-5688
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
AD  - Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, 
      Taiwan.
FAU - Chou, Yu-Chi
AU  - Chou YC
AUID- ORCID: 0000-0002-0783-1339
AD  - Biomedical Translation Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Hsueh, Yi-Ping
AU  - Hsueh YP
AUID- ORCID: 0000-0002-0866-6275
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
FAU - Tsai, Ching-Yen
AU  - Tsai CY
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
FAU - Huang, Pau-Yi
AU  - Huang PY
AD  - Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
FAU - Chang, Sui-Yuan
AU  - Chang SY
AUID- ORCID: 0000-0002-6009-6724
AD  - Department of Clinical Laboratory Sciences and Medical Biotechnology, National 
      Taiwan University College of Medicine, Taipei 100233, Taiwan.
AD  - Department of Laboratory Medicine, National Taiwan University Hospital and 
      National Taiwan University College of Medicine, Taipei 100233, Taiwan.
FAU - Chao, Tai-Ling
AU  - Chao TL
AUID- ORCID: 0000-0002-9815-6702
AD  - Department of Clinical Laboratory Sciences and Medical Biotechnology, National 
      Taiwan University College of Medicine, Taipei 100233, Taiwan.
FAU - Kao, Han-Chieh
AU  - Kao HC
AUID- ORCID: 0000-0001-7996-3448
AD  - Department of Clinical Laboratory Sciences and Medical Biotechnology, National 
      Taiwan University College of Medicine, Taipei 100233, Taiwan.
FAU - Tsai, Ya-Min
AU  - Tsai YM
AUID- ORCID: 0000-0002-2529-8988
AD  - Department of Clinical Laboratory Sciences and Medical Biotechnology, National 
      Taiwan University College of Medicine, Taipei 100233, Taiwan.
FAU - Chen, Yen-Hui
AU  - Chen YH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
FAU - Wu, Chung-Yi
AU  - Wu CY
AUID- ORCID: 0000-0003-2843-2633
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Jan, Jia-Tsrong
AU  - Jan JT
AUID- ORCID: 0000-0002-9721-0017
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Cheng, Ting-Jen Rachel
AU  - Cheng TR
AUID- ORCID: 0000-0003-4297-018X
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Lin, Kuo-I
AU  - Lin KI
AUID- ORCID: 0000-0003-4477-0798
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Ma, Che
AU  - Ma C
AUID- ORCID: 0000-0002-4741-2307
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
FAU - Wong, Chi-Huey
AU  - Wong CH
AUID- ORCID: 0000-0002-9961-7865
AD  - Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
AD  - Department of Chemistry, Scripps Research, La Jolla, CA 92037, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220406
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
RN  - 0 (COVID-19 Vaccines)
RN  - 0 (Polysaccharides)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (spike protein, SARS-CoV-2)
SB  - IM
MH  - Animals
MH  - Antibodies, Neutralizing
MH  - Antibodies, Viral
MH  - COVID-19/prevention & control
MH  - *COVID-19 Vaccines/immunology/metabolism
MH  - Humans
MH  - Mice
MH  - Models, Animal
MH  - *Polysaccharides
MH  - SARS-CoV-2
MH  - *Spike Glycoprotein, Coronavirus
MH  - Vaccination
PMC - PMC9802656
EDAT- 2022/03/02 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/04/06
CRDT- 2022/03/01 12:15
PHST- 2022/03/02 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/03/01 12:15 [entrez]
PHST- 2022/04/06 00:00 [pmc-release]
AID - abm0899 [pii]
AID - 10.1126/scitranslmed.abm0899 [doi]
PST - ppublish
SO  - Sci Transl Med. 2022 Apr 6;14(639):eabm0899. doi: 10.1126/scitranslmed.abm0899. 
      Epub 2022 Apr 6.