sharon sanders
Editor-in-Chief & President
The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism
Brian J. Willett*1, Joe Grove*1, Oscar A MacLean*1, Craig Wilkie*2, Nicola Logan*1, Giuditta De Lorenzo*1 , Wilhelm Furnon*1 , Sam Scott *1 , Maria Manali*1 , Agnieszka Szemiel1 , Shirin Ashraf1 , Elen Vink1, William Harvey 1, Chris Davis 1, Richard Orton1, Joseph Hughes1, Poppy Holland3, Vanessa Silva3, David Pascall4, Kathryn Puxty3, Ana da Silva Filipe1, Gonzalo Yebra5, Sharif Shaaban5, Matthew T. G. Holden5,6, Rute Maria Pinto1, Rory Gunson3, Kate Templeton7, Pablo Murcia1, Arvind H. Patel1, John Haughney**3 , David L. Robertson **1, Massimo Palmarini**1, Surajit Ray**2 , & Emma C. Thomson** 1,3,8 on behalf of the COVID-19 DeplOyed VaccinE (DOVE) Cohort Study investigators, The COVID-19 Genomics UK (COG-UK) Consortium***, the G2P consortium and the Evaluation of Variants Affecting Deployed COVID-19 Vaccines (EVADE) investigators
1. MRC-University of Glasgow Centre for Virus Research, UK, G61 1QH.
2. School of Mathematics, & Statistics, University of Glasgow, UK
3. NHS Greater Glasgow & Clyde, Glasgow, UK
4. MRC Biostatistics Unit, University of Cambridge
5. Public Health Scotland
6. School of Medicine, University of St Andrews
7. NHS Lothian
8. London School of Hygiene and Tropical Medicine, London, UK
Abstract
Vaccination-based exposure to spike protein derived from early SARS-CoV-2 sequences is the key public health strategy against COVID-19. Successive waves of SARS-CoV-2 infections have been characterised by the evolution of highly mutated variants that are more transmissible and that partially evade the adaptive immune response. Omicron is the fifth of these “Variants of Concern” (VOC) and is characterised by a step change in transmission capability, suggesting significant antigenic and biological change. It is characterised by 45 amino acid substitutions, including 30 changes in the spike protein relative to one ofthe earliest sequences, Wuhan-Hu-1, of which 15 occur in the receptorbinding domain, an area strongly associated with humoral immune evasion. In this study, we demonstrate both markedly decreased neutralisation in serology assays and real-world vaccine effectiveness in recipients of two doses of vaccine, with efficacy partially recovered by a third mRNA booster dose.
We also show that immunity from natural infection (without vaccination) is more protective than two doses of vaccine but inferior to three doses. Finally, we demonstrate fundamental changes in the Omicron entry process in vitro, towards TMPRSS2-independent fusion, representing a major shift in the replication properties of SARS-CoV-2. Overall, these findings underlie rapid global transmission and may alter the clinical severity of disease associated with the Omicron variant.
https://www.gla.ac.uk/media/Media_829360_smxx.pdf
Brian J. Willett*1, Joe Grove*1, Oscar A MacLean*1, Craig Wilkie*2, Nicola Logan*1, Giuditta De Lorenzo*1 , Wilhelm Furnon*1 , Sam Scott *1 , Maria Manali*1 , Agnieszka Szemiel1 , Shirin Ashraf1 , Elen Vink1, William Harvey 1, Chris Davis 1, Richard Orton1, Joseph Hughes1, Poppy Holland3, Vanessa Silva3, David Pascall4, Kathryn Puxty3, Ana da Silva Filipe1, Gonzalo Yebra5, Sharif Shaaban5, Matthew T. G. Holden5,6, Rute Maria Pinto1, Rory Gunson3, Kate Templeton7, Pablo Murcia1, Arvind H. Patel1, John Haughney**3 , David L. Robertson **1, Massimo Palmarini**1, Surajit Ray**2 , & Emma C. Thomson** 1,3,8 on behalf of the COVID-19 DeplOyed VaccinE (DOVE) Cohort Study investigators, The COVID-19 Genomics UK (COG-UK) Consortium***, the G2P consortium and the Evaluation of Variants Affecting Deployed COVID-19 Vaccines (EVADE) investigators
1. MRC-University of Glasgow Centre for Virus Research, UK, G61 1QH.
2. School of Mathematics, & Statistics, University of Glasgow, UK
3. NHS Greater Glasgow & Clyde, Glasgow, UK
4. MRC Biostatistics Unit, University of Cambridge
5. Public Health Scotland
6. School of Medicine, University of St Andrews
7. NHS Lothian
8. London School of Hygiene and Tropical Medicine, London, UK
Abstract
Vaccination-based exposure to spike protein derived from early SARS-CoV-2 sequences is the key public health strategy against COVID-19. Successive waves of SARS-CoV-2 infections have been characterised by the evolution of highly mutated variants that are more transmissible and that partially evade the adaptive immune response. Omicron is the fifth of these “Variants of Concern” (VOC) and is characterised by a step change in transmission capability, suggesting significant antigenic and biological change. It is characterised by 45 amino acid substitutions, including 30 changes in the spike protein relative to one ofthe earliest sequences, Wuhan-Hu-1, of which 15 occur in the receptorbinding domain, an area strongly associated with humoral immune evasion. In this study, we demonstrate both markedly decreased neutralisation in serology assays and real-world vaccine effectiveness in recipients of two doses of vaccine, with efficacy partially recovered by a third mRNA booster dose.
We also show that immunity from natural infection (without vaccination) is more protective than two doses of vaccine but inferior to three doses. Finally, we demonstrate fundamental changes in the Omicron entry process in vitro, towards TMPRSS2-independent fusion, representing a major shift in the replication properties of SARS-CoV-2. Overall, these findings underlie rapid global transmission and may alter the clinical severity of disease associated with the Omicron variant.
https://www.gla.ac.uk/media/Media_829360_smxx.pdf
