A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants

  1. Geraldine Nouailles
  2. Julia M. Adler
  3. Peter Pennitz
  4. Stefan Peidli
  5. Gustavo Teixeira Alves
  6. Morris Baumgart
  7. Judith Bushe
  8. Anne Voss
  9. Alina Langenhagen
  10. Fabian Pott
  11. Julia Kazmierski
  12. Cengiz Goekeri
  13. Szandor Simmons
  14. Na Xing
  15. Christine Langner
  16. Ricardo Martin Vidal
  17. Azza Abdelgawad
  18. Susanne Herwig
  19. Günter Cichon
  20. Daniela Niemeyer
  21. Christian Drosten
  22. Christine Goffinet
  23. Markus Landthaler
  24. Nils Blüthgen
  25. Haibo Wu
  26. Martin Witzenrath
  27. Achim D. Gruber
  28. Samantha D. Praktiknjo
  29. Nikolaus Osterrieder
  30. Emanuel Wyler
  31. Dusan Kunec
  32. Jakob Trimpert
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Abstract

Vaccines are a cornerstone in COVID-19 pandemic management. Here, we compare immune responses to and preclinical efficacy of the mRNA vaccine BNT162b2, an adenovirus-vectored spike vaccine, and the live-attenuated-virus vaccine candidate sCPD9 after single and double vaccination in Syrian hamsters. All regimens containing sCPD9 showed superior efficacy. The robust immunity elicited by sCPD9 was evident in a wide range of immune parameters after challenge with heterologous SARS-CoV-2 including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue. Our results demonstrate that use of live-attenuated vaccines may offer advantages over available COVID-19 vaccines, specifically when applied as booster, and may provide a solution for containment of the COVID-19 pandemic.

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