Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Nat Microbiol. 2023 May;8(5):860-874. doi: 10.1038/s41564-023-01352-8. Epub 2023 Apr 3.


Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, 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 after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BNT162 Vaccine
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Cricetinae
  • Humans
  • Mesocricetus
  • Pandemics
  • SARS-CoV-2*
  • Vaccines, Attenuated


  • sCPD9 COVID-19 vaccine
  • Vaccines, Attenuated
  • COVID-19 Vaccines
  • BNT162 Vaccine

Supplementary concepts

  • SARS-CoV-2 variants