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
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.