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

Area of Science:

• Vaccinology
• Immunology
• RNA Therapeutics

Background:

• Self-replicating RNA (srRNA) offers a promising vaccine platform for intradermal delivery.
• Current vaccine strategies often focus on antibody production, but cellular immunity is crucial for pathogen clearance.

Purpose of the Study:

• To develop a temperature-controllable srRNA (c-srRNA) vaccine with a built-in safety mechanism.
• To evaluate the immunogenicity of c-srRNA as an intradermal vaccine against SARS-CoV-2.
• To explore the potential of c-srRNA for developing pan-coronavirus vaccines.

Main Methods:

• Development of a novel srRNA engineered to function at skin temperature (33°C) and inactivate at core body temperature (≥37°C).
• Intradermal vaccination of mice with naked c-srRNA against SARS-CoV-2.
• Assessment of immune responses, including cellular immunity and antibody production.
• Design and evaluation of a pan-coronavirus booster vaccine incorporating conserved viral proteins.

Main Results:

• The c-srRNA vaccine was effective when delivered intradermally without lipid nanoparticles.
• c-srRNA vaccination predominantly induced cellular immunity, with minimal antibody generation.
• Subsequent antigen protein stimulation in vaccinated mice elicited antigen-specific antibodies.
• A pan-coronavirus booster vaccine was designed using conserved spike and nucleoproteins.

Conclusions:

• Temperature-controllable srRNA represents a safe and effective platform for inducing cellular immunity.
• This platform can be leveraged to develop potent vaccines, including pan-coronavirus boosters.
• c-srRNA vaccination strategies may offer a novel route to combat diverse viral pathogens by activating cellular immunity.