Comprehensive Analysis of the Safety Profile of a Single-Stranded RNA Nano-Structure Adjuvant

Abstract

Adjuvants enhance the efficacy of vaccines by stimulating immune response-related gene expression and pathways. Although some adjuvants have been approved for commercial use in human vaccines (e.g., Alum, MF59, and AS03), they might elicit adverse side effects, such as autoimmune diseases. Recently, we developed a novel single-stranded RNA (ssRNA) nano-structure adjuvant, which can stimulate both Th1 and Th2 responses. In this study, we evaluated the safety and toxicological profiles of this ssRNA nano-structure adjuvant in vitro and in vivo. Mice were intramuscularly immunized with the ssRNA nano-structure adjuvant three times, once every 2 weeks. The results indicate no significant differences in hematological and serum biochemistry parameters between the ssRNA-treated groups and the control group. From a histopathological perspective, no evidence of tissue damage was found in any group. The levels of IgE and anti-nuclear antibodies, which are markers of autoimmune disease, were not different between the ssRNA-treated groups and the control group. The findings of this study suggest that the ssRNA nano-structure can be used as a safe adjuvant to increase vaccine efficacies.

Evaluation of glycoprotein E subunit and live attenuated varicella‐zoster virus vaccines formulated with a single‐strand RNA‐based adjuvant

“…42,43 A previous study established that ssRNA adjuvants are relatively safe. 44 Taken together, these results verify that the gE protein produced in this study can be a new VZV protein vaccine candidate. Moreover, the ssRNA derived from CrPV IGR IRES encoding the gE gene, which could express gE in transfected cells, can effectively function as a vaccine adjuvant in a protein-based subunit vaccine by activating humoral and cell-mediated immune responses.…”

“…Nevertheless, the mode of action of AddaVax has not yet been elucidated 42,43 . A previous study established that ssRNA adjuvants are relatively safe 44 …”

MERS-CoV Spike Protein Vaccine and Inactivated Influenza Vaccine Formulated with Single Strand RNA Adjuvant Induce T-Cell Activation through Intranasal Immunization in Mice

“…Additionally, side effects such as autoimmune/inflammatory syndrome induced by adjuvants also occur, requiring further confirmation of safety [30,31]. To compensate for these limitations, RNA adjuvants have recently been developed [19] and applied to MERS and influenza, as they did not accumulate in the body, thus lowering the risk of side effects and effectively increasing the immune response [17,18]. We found that immunization with MERS S protein with RNA adjuvant and alum synergistically induced the humoral immune response and led to balanced Th1/Th2 responses [17].…”

Design and application of nanoparticles as vaccine adjuvants against human corona virus infection

“…11 ) [ 89 , 90 ]. Some atypical vaccine adjuvant materials, such as polymers, RNA, polysaccharides and carbon dots, are currently available, which will not be described one by one [ [91] , [92] , [93] , [94] , [95] ]. Their physicochemical surface properties, self-assembly and aggregation, and the interaction with biological molecules will influence their immune behavior, toxicities and biological effects [ [96] , [97] , [98] , [99] , [100] ].…”