Circular RNA vaccine induces potent T cell responses

Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2302191120. doi: 10.1073/pnas.2302191120. Epub 2023 May 8.

Abstract

Circular RNAs (circRNAs) are a class of RNAs commonly found across eukaryotes and viruses, characterized by their resistance to exonuclease-mediated degradation. Their superior stability compared to linear RNAs, combined with previous work showing that engineered circRNAs serve as efficient protein translation templates, make circRNA a promising candidate for RNA medicine. Here, we systematically examine the adjuvant activity, route of administration, and antigen-specific immunity of circRNA vaccination in mice. Potent circRNA adjuvant activity is associated with RNA uptake and activation of myeloid cells in the draining lymph nodes and transient cytokine release. Immunization of mice with engineered circRNA encoding a protein antigen delivered by a charge-altering releasable transporter induced innate activation of dendritic cells, robust antigen-specific CD8 T cell responses in lymph nodes and tissues, and strong antitumor efficacy as a therapeutic cancer vaccine. These results highlight the potential utility of circRNA vaccines for stimulating potent innate and T cell responses in tissues.

Keywords: CD8 T cells; circular RNA; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigens / metabolism
  • CD8-Positive T-Lymphocytes
  • Immunization* / methods
  • Mice
  • Mice, Inbred C57BL
  • RNA / genetics
  • RNA / metabolism
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Vaccination / methods

Substances

  • RNA, Circular
  • Adjuvants, Immunologic
  • RNA
  • Antigens