1. Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response
- Author
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Hae Li Ko, Kyung Won Kang, Manki Song, Sang-Myeong Lee, Hye-Lim Park, Jae-Ouk Kim, Hye-Jung Kim, Jae-Hwan Nam, Eui-Cheol Shin, Hye Won Kwak, Seung Rok Ryu, Hyo Jung Park, Dae Gwin Jeong, Rhoon-Ho Kim, Min Ho Cha, and Hun Kim
- Subjects
CD4-Positive T-Lymphocytes ,ELISPOT, enzyme-linked immunospot ,dLN, draining lymph node ,T-Lymphocytes ,medicine.medical_treatment ,Tfh, follicular helper T ,CoV, coronavirus ,CD8-Positive T-Lymphocytes ,Antibodies, Viral ,Mice ,0302 clinical medicine ,IRES ,030212 general & internal medicine ,Th1/Th2 ,Alum ,Cells, Cultured ,Adjuvant ,Mice, Inbred BALB C ,TNF, tumor necrosis factor ,RIG-I ,Chemotaxis ,ELISA, enzyme-linked immunosorbent assay ,Flow Cytometry ,CrPV ,Th2, T helper 2 ,NAbs, neutralizing antibodies ,IGR, intergenic region ,Infectious Diseases ,Dicistroviridae ,Molecular Medicine ,Female ,RIG, retinoic acid-inducible gene ,DCs, dendritic cells ,TLR, Toll-like receptor ,PRNT, plaque-reduction neutralization test ,HPV ,030231 tropical medicine ,Enzyme-Linked Immunosorbent Assay ,HPV, human papillomavirus ,Internal Ribosome Entry Sites ,Biology ,CrPV, Cricket paralysis virus ,Article ,03 medical and health sciences ,Th2 Cells ,Immune system ,Adjuvants, Immunologic ,MERS ,Immunity ,Tg, transgenic ,medicine ,Animals ,Humans ,IFN, interferon ,ssRNAs, single-stranded RNAs ,IRESs, internal ribosome entry sites ,General Veterinary ,General Immunology and Microbiology ,fungi ,MERS, Middle East respiratory syndrome ,Public Health, Environmental and Occupational Health ,RNA ,TLR7 ,Th1 Cells ,Vaccine efficacy ,WT, wild-type ,Virology ,Immunity, Innate ,IL, interleukin ,Mice, Inbred C57BL ,PFUs, plaque-forming units ,APCs, Antigen presenting cells ,hPBMCs, human peripheral blood mononuclear cells ,VLP, virus-like particle ,Myd88, myeloid differentiation primary response 88 ,Leukocytes, Mononuclear ,Vaccine ,Leukocyte chemotaxis - 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., 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.
- Published
- 2019