A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS
Copyright policy )A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS
Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.
- Chinese Academy of Medical Sciences & Peking Union Medical College China (People's Republic of)
- Hainan Medical University China (People's Republic of)
- Institute of Microbiology China (People's Republic of)
- Institut Pasteur of Shanghai China (People's Republic of)
- University of Chinese Academy of Sciences China (People's Republic of)
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), COVID-19 Vaccines, Pneumonia, Viral, Peptidyl-Dipeptidase A, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, Mice, Cell Line, Tumor, Chlorocebus aethiops, Animals, Humans, Protein Interaction Domains and Motifs, Pandemics, Mice, Inbred BALB C, COVID-19, Antibodies, Neutralizing, Receptor-binding domain (RBD), Coronavirus, HEK293 Cells, Middle East Respiratory Syndrome Coronavirus, Middle East respiratory syndrome CoV (MERS-CoV), Angiotensin-Converting Enzyme 2, Coronavirus Infections, Vaccine, Protein Binding
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), COVID-19 Vaccines, Pneumonia, Viral, Peptidyl-Dipeptidase A, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, Mice, Cell Line, Tumor, Chlorocebus aethiops, Animals, Humans, Protein Interaction Domains and Motifs, Pandemics, Mice, Inbred BALB C, COVID-19, Antibodies, Neutralizing, Receptor-binding domain (RBD), Coronavirus, HEK293 Cells, Middle East Respiratory Syndrome Coronavirus, Middle East respiratory syndrome CoV (MERS-CoV), Angiotensin-Converting Enzyme 2, Coronavirus Infections, Vaccine, Protein Binding
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).444 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 0.1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.01%
Citations provided by BIP!Popularity provided by BIP!