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Critical Reviews™ in Immunology
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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2019027183
pages 1-14

RNA-Based Adjuvants: Immunoenhancing Effect on Antiviral Vaccines and Regulatory Considerations

Annett Ziegler
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research (joint venture between the Hannover Medical School and Helmholtz Centre for Infection Research), 30625 Hannover, Germany
Thomas Hinz
Division Immunology, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, 63225 Langen, Germany
Ulrich Kalinke
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research (joint venture between the Hannover Medical School and Helmholtz Centre for Infection Research), 30625 Hannover, Germany; Cluster of Excellence: Resolving Infection Susceptibility (RESIST), Hannover Medical School, 30625 Hannover, Germany

ABSTRACT

During the last decade, a wide variety of cellular RNA sensors and structural characteristics of their agonists have been identified. On the basis of this knowledge, RNA formulations were developed as innovative adjuvant candidates. In contrast to DNA, RNA does not have genotoxic potential and is rapidly degraded. In many aspects, RNA mimics viral infections and induces considerably strong immune responses. Additionally, RNA-based adjuvants can be designed so that distinct RNA sensors can be triggered according to requirements of individual vaccines. Furthermore, RNA can be synthesized in vitro in a cell-free system, and recent developments in formulation technology have led to reduced RNA degradation within the body. These features qualify RNA as a promising adjuvant candidate. Here, we discuss latest developments in the field of RNA-based adjuvants and highlight differences between human and mouse nucleic acid sensors, which constitute a challenge in the development of RNA-based adjuvants. Finally, we discuss how RNA-based adjuvants are currently handled with regard to regulatory requirements.

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