Frontiers in Immunology (Feb 2025)

Intradermal delivery of SARS-CoV-2 RBD3-Fc mRNA vaccines via a needle-free injection system induces robust immune responses in rats

  • Cenrong Wang,
  • Xin Tang,
  • Xin Tang,
  • Chenghan Jiang,
  • Yu Zhang,
  • Bo Han,
  • Yi Sun,
  • Jianfeng Guo,
  • Hanyu Peng,
  • Zihan Wang,
  • Yipeng Wang,
  • Jialu Zhang,
  • Yong Zhang,
  • Yong Zhang,
  • Chunlai Jiang,
  • Chunlai Jiang,
  • Chunlai Jiang

DOI
https://doi.org/10.3389/fimmu.2025.1530736
Journal volume & issue
Vol. 16

Abstract

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IntroductionNeedle-free injection system (NFIS) is easy to operate and can decrease needle phobia. Besides, NFIS can increase the interaction of antigens in a more dispersed manner with immune cell at local injection site, which may improve the immune responses of mRNA vaccines. Although SARS-CoV-2 mRNA vaccines have great success, universal vaccines are urgently needed. Delivering universal mRNA vaccines by NFIS is preferred to combat COVID-19.MethodsRBD3-Fc mRNA expressing BA.4, Delta, and prototype RBD, and human IgG Fc with YTE mutation was designed and synthesized. The safety and immune responses of universal RBD3-Fc naked mRNA and mRNA-LNP vaccines delivered intradermally using NFIS (named GV-01) and intramuscularly via needles were evaluated and compared in rats.ResultsThe prime-boost regimen administered by two routes resulted in potent immune responses and intradermal delivery displays comparable or better performance in terms of binding antibodies, neutralizing antibodies and T cell responses. Naked mRNA vaccines were functional, but less effective than mRNA-LNP vaccines.DiscussionThe above results suggest that RBD3-Fc vaccines are safe and immunogenic and NFIS can be used as an alternative to needles/syringes for the inoculation of mRNA-LNP vaccines to elicit robust systematic immune responses.

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