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iScience . Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity

tetano

Editor, Senior Moderator
iScience


. 2023 Mar 5;26(4):106335.
doi: 10.1016/j.isci.2023.106335. eCollection 2023 Apr 21.
Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity


Tomokazu Amano[SUP] 1 [/SUP], Hong Yu[SUP] 1 [/SUP], Misa Amano[SUP] 1 [/SUP], Erica Leyder[SUP] 1 [/SUP], Maria Badiola[SUP] 1 [/SUP], Priyanka Ray[SUP] 1 [/SUP], Jiyoung Kim[SUP] 1 [/SUP], Akihiro C Ko[SUP] 1 [/SUP], Achouak Achour[SUP] 2 [/SUP], Nan-Ping Weng[SUP] 2 [/SUP], Efrat Kochba[SUP] 3 [/SUP], Yotam Levin[SUP] 3 [/SUP], Minoru S H Ko[SUP] 1 [/SUP]



Affiliations

Abstract

Intradermal delivery of self-replicating RNA (srRNA) is a promising vaccine platform. We have developed an srRNA that functions optimally at around 33°C (skin temperature) and is inactivated at or above 37°C (core body temperature) as a safety switch. This temperature-controllable srRNA (c-srRNA), when tested as an intradermal vaccine against SARS-CoV-2, functions when injected naked without lipid nanoparticles. Unlike most currently available vaccines, c-srRNA vaccines predominantly elicit cellular immunity with little or no antibody production. Interestingly, c-srRNA-vaccinated mice produced antigen-specific antibodies upon subsequent stimulation with antigen protein. Antigen-specific antibodies were also produced when B cell stimulation using antigen protein was followed by c-srRNA booster vaccination. We have thus designed a pan-coronavirus booster vaccine that incorporates both spike-receptor-binding domains as viral surface proteins and evolutionarily conserved nucleoproteins as viral internal proteins, from both severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus. c-srRNA may provide a route to activate cellular immunity against a wide variety of pathogens.

Keywords: Immunity; Molecular biology; Virology.
 
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