Cell
Volume 185, Issue 10, 12 May 2022, Pages 1728-1744.e16
Journal home page for Cell

Article
Circular RNA vaccines against SARS-CoV-2 and emerging variants

https://doi.org/10.1016/j.cell.2022.03.044Get rights and content
Under a Creative Commons license
open access

Highlights

  • Highly stable circRNA vaccines induce potent humoral and cellular immune responses

  • CircRNA vaccines elicit a high proportion of neutralizing antibodies

  • CircRNA vaccines enable effective protection against SARS-CoV-2 in mice and monkeys

  • CircRNARBD-Delta vaccine provides broad-spectrum protection against SARS-CoV-2 VOCs

Summary

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.

Keywords

SARS-CoV-2
Omicron
circular RNA
Delta
vaccine
variant of concern
circRNA vaccine
mRNA vaccine
COVID-19

Data and code availability

All data and materials presented in this manuscript are available from the corresponding author (W.W.) upon a reasonable request under a completed Material Transfer Agreement. This paper does not report original code. Any additional information required to reanalyze the data reported in this work paper is available from the lead contact upon request. Additional Supplemental Items are available from Mendeley Data at https://doi.org/10.17632/vp2fskswfv.1.

Cited by (0)

9

These authors contributed equally

10

Lead contact