BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2

  1. Annette B. Vogel
  2. Isis Kanevsky
  3. Ye Che
  4. Kena A. Swanson
  5. Alexander Muik
  6. Mathias Vormehr
  7. Lena M. Kranz
  8. Kerstin C. Walzer
  9. Stephanie Hein
  10. Alptekin Güler
  11. Jakob Loschko
  12. Mohan S. Maddur
  13. Ayuko Ota-Setlik
  14. Kristin Tompkins
  15. Journey Cole
  16. Bonny G. Lui
  17. Thomas Ziegenhals
  18. Arianne Plaschke
  19. David Eisel
  20. Sarah C. Dany
  21. Stephanie Fesser
  22. Stephanie Erbar
  23. Ferdia Bates
  24. Diana Schneider
  25. Bernadette Jesionek
  26. Bianca Sänger
  27. Ann-Kathrin Wallisch
  28. Yvonne Feuchter
  29. Hanna Junginger
  30. Stefanie A. Krumm
  31. André P. Heinen
  32. Petra Adams-Quack
  33. Julia Schlereth
  34. Stefan Schille
  35. Christoph Kröner
  36. Ramón de la Caridad Güimil Garcia
  37. Thomas Hiller
  38. Leyla Fischer
  39. Rani S. Sellers
  40. Shambhunath Choudhary
  41. Olga Gonzalez
  42. Fulvia Vascotto
  43. Matthew R. Gutman
  44. Jane A. Fontenot
  45. Shannan Hall-Ursone
  46. Kathleen Brasky
  47. Matthew C. Griffor
  48. Seungil Han
  49. Andreas A.H. Su
  50. Joshua A. Lees
  51. Nicole L. Nedoma
  52. Ellene H. Mashalidis
  53. Parag V. Sahasrabudhe
  54. Charles Y. Tan
  55. Danka Pavliakova
  56. Guy Singh
  57. Camila Fontes-Garfias
  58. Michael Pride
  59. Ingrid L. Scully
  60. Tara Ciolino
  61. Jennifer Obregon
  62. Michal Gazi
  63. Ricardo Carrion
  64. Kendra J. Alfson
  65. Warren V. Kalina
  66. Deepak Kaushal
  67. Pei-Yong Shi
  68. Thorsten Klamp
  69. Corinna Rosenbaum
  70. Andreas N. Kuhn
  71. Özlem Türeci
  72. Philip R. Dormitzer
  73. Kathrin U. Jansen
  74. Ugur Sahin
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Abstract

A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20% of the P 2S trimers are in the two-RBD ‘down,’ one-RBD ‘up’ state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4 + and IFNγ + CD8 + T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial ( <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04380701">NCT04380701</ext-link> , <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04368728">NCT04368728</ext-link> ).

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