RT Journal Article
SR Electronic
T1 Cutaneous jet-injection of naked mRNA vaccine induces robust immune responses without systemic vaccine spillage
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.27.530188
DO 10.1101/2023.02.27.530188
A1 Saed Abbasi
A1 Miki Matsui-Masai
A1 Akimasa Hayashi
A1 Theofilus A. Tockary
A1 Shiro Akinaga
A1 Kazunori Kataoka
A1 Satoshi Uchida
YR 2023
UL http://biorxiv.org/content/early/2023/02/27/2023.02.27.530188.abstract
AB Locally injected lipid nanoparticle (LNP)-based mRNA vaccines migrate systemically, which could raise safety concerns. From a mechanistic viewpoint, whether local or systemic antigen expression contributes to the vaccine effects remains unclear. Herein, we localized the antigen protein expression using naked mRNA and drastically improved the delivery efficiency in the skin by jet injection. Consequently, jet-injected naked mRNA outperformed a widely-used LNP in humoral immunity induction at the highest tolerable mRNA doses of each formulation in mice. A mechanistic investigation suggests that antigenpresenting cells taking up antigens at the jet-injection site of naked mRNA migrate to draining lymph nodes, enabling robust immunization without systemic mRNA distribution. Ultimately, jet injection of SARS-CoV-2 spike mRNA provided efficient antibody responses, neutralizing potential and cellular immunity in rodents and non-human primates with no reactogenicity. Conclusively, naked mRNA jet injection is a robust, tolerable, and simple vaccine candidate.Competing Interest StatementSa.A., M.M., H.A., K.K., and S.U. have filed a patent application related to this study, and NanoCarrier Ltd. (M.M., Sh.A.) holds a right to the patent. K.K. is a founder and a member of the Board of NanoCarrier Ltd. M.M. is an employee of NanoCarrier Ltd. Sh.A. is a CEO and CSO of NanoCarrier Ltd.