Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response. Issue 36 (23rd August 2019)

• Record Type: Journal Article
• Authors: Kwak, Hye Won; Park, Hyo-Jung; Ko, Hae Li; Park, Hyelim; Cha, Min Ho; Lee, Sang-Myeong; Kang, Kyung Won; Kim, Rhoon-Ho; Ryu, Seung Rok; Kim, Hye-Jung; Kim, Jae-Ouk; Song, Manki; Kim, Hun; Jeong, Dae Gwin; Shin, Eui-Cheol; Nam, Jae-Hwan
• Is Part Of: Vaccine. Volume 37:Issue 36(2019)
• Page Start: 5191
• Page End: 5202
• Publication Date: 2019-08-23
• Subjects: MERS -- HPV -- CrPV -- IRES -- RNA -- Adjuvant -- Vaccine -- Th1/Th2 -- Alum; APCs Antigen presenting cells -- DCs dendritic cells -- Th2 T helper 2 -- TLR Toll-like receptor -- IFN interferon -- ssRNAs single-stranded RNAs -- IL interleukin -- Tfh follicular helper T -- RIG retinoic acid-inducible gene -- IRESs internal ribosome entry sites -- CrPV Cricket paralysis virus -- IGR intergenic region -- MERS Middle East respiratory syndrome -- CoV coronavirus -- HPV human papillomavirus -- dLN draining lymph node -- NAbs neutralizing antibodies -- VLP virus-like particle -- Tg transgenic -- WT wild-type -- ELISA enzyme-linked immunosorbent assay -- PRNT plaque-reduction neutralization test -- PFUs plaque-forming units -- ELISPOT enzyme-linked immunospot -- hPBMCs human peripheral blood mononuclear cells -- TNF tumor necrosis factor -- Myd88 myeloid differentiation primary response 88; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.07.070
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: RNA adjuvant was developed from the CrPV intergenic region IRES. The RNA adjuvant functioned as an adjuvant with protein-based vaccines. The RNA adjuvant increased vaccine efficacy and induced balanced Th1/Th2 response. The RNA adjuvant enhanced APC chemotaxis. Abstract: 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 live-attenuated 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.