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A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses.
Tan, Tiong Kit; Rijal, Pramila; Rahikainen, Rolle; Keeble, Anthony H; Schimanski, Lisa; Hussain, Saira; Harvey, Ruth; Hayes, Jack W P; Edwards, Jane C; McLean, Rebecca K; Martini, Veronica; Pedrera, Miriam; Thakur, Nazia; Conceicao, Carina; Dietrich, Isabelle; Shelton, Holly; Ludi, Anna; Wilsden, Ginette; Browning, Clare; Zagrajek, Adrian K; Bialy, Dagmara; Bhat, Sushant; Stevenson-Leggett, Phoebe; Hollinghurst, Philippa; Tully, Matthew; Moffat, Katy; Chiu, Chris; Waters, Ryan; Gray, Ashley; Azhar, Mehreen; Mioulet, Valerie; Newman, Joseph; Asfor, Amin S; Burman, Alison; Crossley, Sylvia; Hammond, John A; Tchilian, Elma; Charleston, Bryan; Bailey, Dalan; Tuthill, Tobias J; Graham, Simon P; Duyvesteyn, Helen M E; Malinauskas, Tomas; Huo, Jiandong; Tree, Julia A; Buttigieg, Karen R; Owens, Raymond J; Carroll, Miles W; Daniels, Rodney S; McCauley, John W.
  • Tan TK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK. tiong.tan@rdm.ox.ac.uk.
  • Rijal P; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK.
  • Rahikainen R; Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK.
  • Keeble AH; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
  • Schimanski L; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
  • Hussain S; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK.
  • Harvey R; Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK.
  • Hayes JWP; Worldwide Influenza Centre, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
  • Edwards JC; Worldwide Influenza Centre, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
  • McLean RK; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Martini V; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Pedrera M; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Thakur N; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Conceicao C; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Dietrich I; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Shelton H; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Ludi A; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Wilsden G; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Browning C; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Zagrajek AK; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Bialy D; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Bhat S; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Stevenson-Leggett P; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Hollinghurst P; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Tully M; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Moffat K; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Chiu C; Department of Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK.
  • Waters R; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Gray A; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Azhar M; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Mioulet V; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Newman J; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Asfor AS; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Burman A; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Crossley S; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Hammond JA; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Tchilian E; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Charleston B; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Bailey D; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Tuthill TJ; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Graham SP; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Duyvesteyn HME; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Malinauskas T; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Huo J; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, UK.
  • Tree JA; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.
  • Buttigieg KR; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.
  • Owens RJ; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.
  • Carroll MW; Rutherford Appleton Laboratory, Protein Production UK, Research Complex at Harwell, and Rosalind Franklin Institute, Harwell, Didcot, OX11 0FA, UK.
  • Daniels RS; National Infection Service, Public Health England, Porton Down, Salisbury, SP4 0JG, UK.
  • McCauley JW; National Infection Service, Public Health England, Porton Down, Salisbury, SP4 0JG, UK.
Nat Commun ; 12(1): 542, 2021 01 22.
Article in English | MEDLINE | ID: covidwho-1044339
ABSTRACT
There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptides / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Experimental Studies / Prognostic study Topics: Vaccines Limits: Animals Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-020-20654-7

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptides / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Experimental Studies / Prognostic study Topics: Vaccines Limits: Animals Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-020-20654-7