Development of an RNA Expression Platform Controlled by Viral Internal Ribosome Entry Sites

Ko, Hae Li; Park, Hyo-Jung; Kim, Jihye; Kim, Heon; Youn, Hyewon; Nam, Jae Hwan

doi:10.4014/jmb.1811.11019

Cited by 17 publications

(26 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This transient induction of genes by the RNA adjuvant may be evidence of vaccine safety. Similarly, a previous report demonstrated the rapid disappearance of the RNA platform within 24 h after injection [23]. We did not observe any adverse effects, such as autoimmune symptoms, changes in liver function, or organ damage, in the RNA adjuvant-immunized mice, even at a higher dose (200 mg/-mouse) (data not shown).…”

Section: Discussionsupporting

confidence: 88%

“…In this study, we demonstrated the adjuvant effect of CrPV-IGR IRES-derived ssRNA [23] using protein-based vaccines. The RNA adjuvant induced the expression of genes related to the innate immune response (IFN and TLR-Myd88), T cell activation, and leukocyte chemotaxis similar to poly(I:C) in hPBMCs; however, the induction levels were lower than those by poly(I:C), and most genes returned to normal levels within 24 h (Fig.…”

Section: Discussionmentioning

confidence: 89%

“…The DNA platform was designed using the IGR IRES and SV40 late-polyadenylation signal sequences ( Supplementary Fig. 1) [23]. DNA templates were linearized with NotI.…”

Section: In Vitro Transcription and Rna Purificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…We previously developed novel ssRNA-expression platforms from several viral internal ribosome entry sites (IRESs) [23]. In this study, we investigated the adjuvant effects of ssRNAs (RNA adjuvant) derived from the Cricket paralysis virus (CrPV) intergenic region (IGR) IRES [23]. We formulated the RNA adjuvant with protein-subunit vaccine for Middle East Respiratory Syndrome (MERS)-coronavirus (CoV) and virus-like particle vaccine for human papillomavirus (HPV) and showed that the RNA adjuvant induced a balanced Th1/Th2 response and innate immunity.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response

Kwak

Park

et al. 2019

Vaccine

Self Cite

View full text Add to dashboard Cite

Keywords:MERS HPV CrPV IRES RNA Adjuvant Vaccine Th1/Th2 Alum a b s t r a c t An ideal adjuvant should increase vaccine efficacy through balanced Th1/Th2 responses and be safe to use. Recombinant protein-based vaccines are usually formulated with aluminum (alum)-based adjuvants to ensure an adequate immune response. However, use of alum triggers a Th2-biased immune induction, and hence is not optimal. Although the adjuvanticity of RNA has been reported, a systematic and overall investigation on its efficacy is lacking. We found that single strand RNA (termed RNA adjuvant) derived from cricket paralysis virus intergenic region internal ribosome entry site induced the expression of various adjuvant-function-related genes, such as type 1 and 2 interferon (IFN) and toll-like receptor (TLR), T cell activation, and leukocyte chemotaxis in human peripheral blood mononuclear cells; furthermore, its innate and IFN transcriptome profile patterns were similar to those of a live-attenuated yellow fever vaccine. This suggests that protein-based vaccines formulated using RNA adjuvant function as liveattenuated vaccines. Application of the RNA adjuvant in mouse enhanced the efficacy of Middle East respiratory syndrome spike protein, a protein-subunit vaccine and human papillomavirus L1 protein, a virus-like particle vaccine, by activating innate immune response through TLR7 and enhancing pAPC chemotaxis, leading to a balanced Th1/Th2 responses. Moreover, the combination of alum and the RNA adjuvant synergistically induced humoral and cellular immune responses and endowed long-term immunity. Therefore, RNA adjuvants have broad applicability and can be used with all conventional vaccines to improve vaccine efficacy qualitatively and quantitively.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 89%

“…The DNA platform was designed using the IGR IRES and SV40 late-polyadenylation signal sequences ( Supplementary Fig. 1) [23]. DNA templates were linearized with NotI.…”

Section: In Vitro Transcription and Rna Purificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response

Kwak

Park

et al. 2019

Vaccine

Self Cite

View full text Add to dashboard Cite

show abstract

Nanoformulated Single‐Stranded RNA‐Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen‐Presenting Cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

As agonists of TLR7/8, single‐stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off‐target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA‐based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA‐O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen‐presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA‐O may increase the efficacy of ssRNA‐based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.

show abstract

Nanoformulated Single‐Stranded RNA‐Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen‐Presenting Cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Development of an RNA Expression Platform Controlled by Viral Internal Ribosome Entry Sites

Cited by 17 publications

References 49 publications

Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response

Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response

Nanoformulated Single‐Stranded RNA‐Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen‐Presenting Cells

Nanoformulated Single‐Stranded RNA‐Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen‐Presenting Cells

Contact Info

Product

Resources

About