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

Tomokazu Amano; Hong Yu; Misa Amano; Erica Leyder; Maria Badiola; Priyanka Ray; Jiyoung Kim; Akihiro C Ko; Achouak Achour; Nan-Ping Weng; Efrat Kochba; Yotam Levin; Minoru S H Ko

doi:10.1016/j.isci.2023.106335

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

iScience. 2023 Mar 5;26(4):106335. doi: 10.1016/j.isci.2023.106335. eCollection 2023 Apr 21.

Authors

Affiliations

¹ Elixirgen Therapeutics, Inc., Baltimore, MD, USA.
² Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD, USA.
³ NanoPass Technologies Ltd., Ness Ziona, Israel.

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.