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

•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 vac... Full description

Journal Title: Vaccine 2019, Vol.37 (36), p.5191-5202
Main Author: Kwak, Hye Won
Other Authors: 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
Format: Electronic Article Electronic Article
Language: English
Subjects:
CoV
DCs
dLN
HPV
RNA
str
Tfh
Th1
Th2
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/31371226
Zum Text:
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7115557
title: Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response
format: Article
creator:
  • 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
subjects:
  • Adjuvant
  • Adjuvanticity
  • Adjuvants
  • Adjuvants, Immunologic - metabolism
  • Alum
  • Aluminum
  • Animals
  • Antibodies, Viral - immunology
  • Antibodies, Viral - metabolism
  • Antigen presenting cells
  • Antigens
  • APCs
  • APCs, Antigen presenting cells
  • Article
  • Biological response modifiers
  • CD4-Positive T-Lymphocytes - metabolism
  • CD8-Positive T-Lymphocytes - metabolism
  • Cell activation
  • Cells, Cultured
  • Chemotaxis
  • Chemotaxis - genetics
  • Chemotaxis - physiology
  • coronavirus
  • CoV
  • CoV, coronavirus
  • Cricket paralysis virus
  • CrPV
  • CrPV, Cricket paralysis virus
  • Cytokines
  • DCs
  • DCs, dendritic cells
  • Dendritic cells
  • Dicistroviridae - genetics
  • Dicistroviridae - immunology
  • Dicistroviridae - pathogenicity
  • dLN
  • dLN, draining lymph node
  • draining lymph node
  • ed RNAs
  • Effectiveness
  • ELISA, enzyme-linked immunosorbent assay
  • ELISPOT, enzyme-linked immunospot
  • enzyme
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • follicular helper T
  • forming units
  • Gene expression
  • Genes
  • Genetic engineering
  • hPBMCs
  • hPBMCs, human peripheral blood mononuclear cells
  • HPV
  • HPV, human papillomavirus
  • Human papillomavirus
  • human peripheral blood mononuclear cells
  • Humans
  • IFN, interferon
  • IGR, intergenic region
  • IL, interleukin
  • Immune response
  • Immune response (humoral)
  • Immune system
  • Immunity
  • Immunity, Innate - physiology
  • inducible gene
  • Influenza
  • Innate immunity
  • Interferon
  • intergenic region
  • interleukin
  • Internal ribosome entry site
  • internal ribosome entry sites
  • Internal Ribosome Entry Sites - genetics
  • IRES
  • IRESs
  • IRESs, internal ribosome entry sites
  • L1 protein
  • Laboratory animals
  • Leukocytes
  • Leukocytes (mononuclear)
  • Leukocytes, Mononuclear - metabolism
  • like particle
  • like receptor
  • linked immunosorbent assay
  • linked immunospot
  • Lymphocytes
  • Lymphocytes T
  • MERS
  • MERS, Middle East respiratory syndrome
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Middle East respiratory syndrome
  • Myd88
  • Myd88, myeloid differentiation primary response 88
  • myeloid differentiation primary response 88
  • NAbs
  • NAbs, neutralizing antibodies
  • neutralizing antibodies
  • Papillomavirus infections
  • Paralysis
  • Peripheral blood mononuclear cells
  • PFUs
  • PFUs, plaque-forming units
  • plaque
  • PRNT, plaque-reduction neutralization test
  • Proteins
  • Recombinant proteins
  • reduction neutralization test
  • Respiratory diseases
  • retinoic acid
  • Ribonucleic acid
  • RIG, retinoic acid-inducible gene
  • RNA
  • RNA - metabolism
  • single
  • Spike protein
  • ssRNAs
  • ssRNAs, single-stranded RNAs
  • str
  • T cells
  • T helper 2
  • T-Lymphocytes - metabolism
  • Tfh
  • Tfh, follicular helper T
  • Tg, transgenic
  • Th1
  • Th1 Cells - metabolism
  • Th1/Th2
  • Th2
  • Th2 Cells - metabolism
  • Th2, T helper 2
  • TLR, Toll-like receptor
  • TLR7 protein
  • TNF, tumor necrosis factor
  • Toll
  • Toll-like receptors
  • transgenic
  • tumor necrosis factor
  • type
  • Vaccine
  • Vaccine efficacy
  • Vaccines
  • Vector-borne diseases
  • virus
  • Virus-like particles
  • Viruses
  • VLP, virus-like particle
  • wild
  • WT, wild-type
  • Yellow fever
ispartof: Vaccine, 2019, Vol.37 (36), p.5191-5202
description: •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.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleCricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response
sourceAlma/SFX Local Collection
creatorKwak, 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
creatorcontribKwak, 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
description•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.
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0ISSN: 0264-410X
1EISSN: 1873-2518
2DOI: 10.1016/j.vaccine.2019.07.070
3PMID: 31371226
languageeng
publisherNetherlands: Elsevier Ltd
subjectAdjuvant ; Adjuvanticity ; Adjuvants ; Adjuvants, Immunologic - metabolism ; Alum ; Aluminum ; Animals ; Antibodies, Viral - immunology ; Antibodies, Viral - metabolism ; Antigen presenting cells ; Antigens ; APCs ; APCs, Antigen presenting cells ; Article ; Biological response modifiers ; CD4-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - metabolism ; Cell activation ; Cells, Cultured ; Chemotaxis ; Chemotaxis - genetics ; Chemotaxis - physiology ; coronavirus ; CoV ; CoV, coronavirus ; Cricket paralysis virus ; CrPV ; CrPV, Cricket paralysis virus ; Cytokines ; DCs ; DCs, dendritic cells ; Dendritic cells ; Dicistroviridae - genetics ; Dicistroviridae - immunology ; Dicistroviridae - pathogenicity ; dLN ; dLN, draining lymph node ; draining lymph node ; ed RNAs ; Effectiveness ; ELISA, enzyme-linked immunosorbent assay ; ELISPOT, enzyme-linked immunospot ; enzyme ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; follicular helper T ; forming units ; Gene expression ; Genes ; Genetic engineering ; hPBMCs ; hPBMCs, human peripheral blood mononuclear cells ; HPV ; HPV, human papillomavirus ; Human papillomavirus ; human peripheral blood mononuclear cells ; Humans ; IFN, interferon ; IGR, intergenic region ; IL, interleukin ; Immune response ; Immune response (humoral) ; Immune system ; Immunity ; Immunity, Innate - physiology ; inducible gene ; Influenza ; Innate immunity ; Interferon ; intergenic region ; interleukin ; Internal ribosome entry site ; internal ribosome entry sites ; Internal Ribosome Entry Sites - genetics ; IRES ; IRESs ; IRESs, internal ribosome entry sites ; L1 protein ; Laboratory animals ; Leukocytes ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - metabolism ; like particle ; like receptor ; linked immunosorbent assay ; linked immunospot ; Lymphocytes ; Lymphocytes T ; MERS ; MERS, Middle East respiratory syndrome ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Middle East respiratory syndrome ; Myd88 ; Myd88, myeloid differentiation primary response 88 ; myeloid differentiation primary response 88 ; NAbs ; NAbs, neutralizing antibodies ; neutralizing antibodies ; Papillomavirus infections ; Paralysis ; Peripheral blood mononuclear cells ; PFUs ; PFUs, plaque-forming units ; plaque ; PRNT, plaque-reduction neutralization test ; Proteins ; Recombinant proteins ; reduction neutralization test ; Respiratory diseases ; retinoic acid ; Ribonucleic acid ; RIG, retinoic acid-inducible gene ; RNA ; RNA - metabolism ; single ; Spike protein ; ssRNAs ; ssRNAs, single-stranded RNAs ; str ; T cells ; T helper 2 ; T-Lymphocytes - metabolism ; Tfh ; Tfh, follicular helper T ; Tg, transgenic ; Th1 ; Th1 Cells - metabolism ; Th1/Th2 ; Th2 ; Th2 Cells - metabolism ; Th2, T helper 2 ; TLR, Toll-like receptor ; TLR7 protein ; TNF, tumor necrosis factor ; Toll ; Toll-like receptors ; transgenic ; tumor necrosis factor ; type ; Vaccine ; Vaccine efficacy ; Vaccines ; Vector-borne diseases ; virus ; Virus-like particles ; Viruses ; VLP, virus-like particle ; wild ; WT, wild-type ; Yellow fever
ispartofVaccine, 2019, Vol.37 (36), p.5191-5202
rights
02019 Elsevier Ltd
1Copyright © 2019 Elsevier Ltd. All rights reserved.
2COPYRIGHT 2019 Elsevier B.V.
32019. Elsevier Ltd
42019 Elsevier Ltd. All rights reserved. 2019 Elsevier Ltd
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0Kwak, Hye Won
1Park, Hyo-Jung
2Ko, Hae Li
3Park, Hyelim
4Cha, Min Ho
5Lee, Sang-Myeong
6Kang, Kyung Won
7Kim, Rhoon-Ho
8Ryu, Seung Rok
9Kim, Hye-Jung
10Kim, Jae-Ouk
11Song, Manki
12Kim, Hun
13Jeong, Dae Gwin
14Shin, Eui-Cheol
15Nam, Jae-Hwan
title
0Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response
1Vaccine
addtitleVaccine
description•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.
subject
0Adjuvant
1Adjuvanticity
2Adjuvants
3Adjuvants, Immunologic - metabolism
4Alum
5Aluminum
6Animals
7Antibodies, Viral - immunology
8Antibodies, Viral - metabolism
9Antigen presenting cells
10Antigens
11APCs
12APCs, Antigen presenting cells
13Article
14Biological response modifiers
15CD4-Positive T-Lymphocytes - metabolism
16CD8-Positive T-Lymphocytes - metabolism
17Cell activation
18Cells, Cultured
19Chemotaxis
20Chemotaxis - genetics
21Chemotaxis - physiology
22coronavirus
23CoV
24CoV, coronavirus
25Cricket paralysis virus
26CrPV
27CrPV, Cricket paralysis virus
28Cytokines
29DCs
30DCs, dendritic cells
31Dendritic cells
32Dicistroviridae - genetics
33Dicistroviridae - immunology
34Dicistroviridae - pathogenicity
35dLN
36dLN, draining lymph node
37draining lymph node
38ed RNAs
39Effectiveness
40ELISA, enzyme-linked immunosorbent assay
41ELISPOT, enzyme-linked immunospot
42enzyme
43Enzyme-Linked Immunosorbent Assay
44Female
45Flow Cytometry
46follicular helper T
47forming units
48Gene expression
49Genes
50Genetic engineering
51hPBMCs
52hPBMCs, human peripheral blood mononuclear cells
53HPV
54HPV, human papillomavirus
55Human papillomavirus
56human peripheral blood mononuclear cells
57Humans
58IFN, interferon
59IGR, intergenic region
60IL, interleukin
61Immune response
62Immune response (humoral)
63Immune system
64Immunity
65Immunity, Innate - physiology
66inducible gene
67Influenza
68Innate immunity
69Interferon
70intergenic region
71interleukin
72Internal ribosome entry site
73internal ribosome entry sites
74Internal Ribosome Entry Sites - genetics
75IRES
76IRESs
77IRESs, internal ribosome entry sites
78L1 protein
79Laboratory animals
80Leukocytes
81Leukocytes (mononuclear)
82Leukocytes, Mononuclear - metabolism
83like particle
84like receptor
85linked immunosorbent assay
86linked immunospot
87Lymphocytes
88Lymphocytes T
89MERS
90MERS, Middle East respiratory syndrome
91Mice
92Mice, Inbred BALB C
93Mice, Inbred C57BL
94Middle East respiratory syndrome
95Myd88
96Myd88, myeloid differentiation primary response 88
97myeloid differentiation primary response 88
98NAbs
99NAbs, neutralizing antibodies
100neutralizing antibodies
101Papillomavirus infections
102Paralysis
103Peripheral blood mononuclear cells
104PFUs
105PFUs, plaque-forming units
106plaque
107PRNT, plaque-reduction neutralization test
108Proteins
109Recombinant proteins
110reduction neutralization test
111Respiratory diseases
112retinoic acid
113Ribonucleic acid
114RIG, retinoic acid-inducible gene
115RNA
116RNA - metabolism
117single
118Spike protein
119ssRNAs
120ssRNAs, single-stranded RNAs
121str
122T cells
123T helper 2
124T-Lymphocytes - metabolism
125Tfh
126Tfh, follicular helper T
127Tg, transgenic
128Th1
129Th1 Cells - metabolism
130Th1/Th2
131Th2
132Th2 Cells - metabolism
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143Vaccine efficacy
144Vaccines
145Vector-borne diseases
146virus
147Virus-like particles
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151WT, wild-type
152Yellow fever
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1Park, Hyo-Jung
2Ko, Hae Li
3Park, Hyelim
4Cha, Min Ho
5Lee, Sang-Myeong
6Kang, Kyung Won
7Kim, Rhoon-Ho
8Ryu, Seung Rok
9Kim, Hye-Jung
10Kim, Jae-Ouk
11Song, Manki
12Kim, Hun
13Jeong, Dae Gwin
14Shin, Eui-Cheol
15Nam, Jae-Hwan
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creationdate20190823
titleCricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response
authorKwak, 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
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topic
0Adjuvant
1Adjuvanticity
2Adjuvants
3Adjuvants, Immunologic - metabolism
4Alum
5Aluminum
6Animals
7Antibodies, Viral - immunology
8Antibodies, Viral - metabolism
9Antigen presenting cells
10Antigens
11APCs
12APCs, Antigen presenting cells
13Article
14Biological response modifiers
15CD4-Positive T-Lymphocytes - metabolism
16CD8-Positive T-Lymphocytes - metabolism
17Cell activation
18Cells, Cultured
19Chemotaxis
20Chemotaxis - genetics
21Chemotaxis - physiology
22coronavirus
23CoV
24CoV, coronavirus
25Cricket paralysis virus
26CrPV
27CrPV, Cricket paralysis virus
28Cytokines
29DCs
30DCs, dendritic cells
31Dendritic cells
32Dicistroviridae - genetics
33Dicistroviridae - immunology
34Dicistroviridae - pathogenicity
35dLN
36dLN, draining lymph node
37draining lymph node
38ed RNAs
39Effectiveness
40ELISA, enzyme-linked immunosorbent assay
41ELISPOT, enzyme-linked immunospot
42enzyme
43Enzyme-Linked Immunosorbent Assay
44Female
45Flow Cytometry
46follicular helper T
47forming units
48Gene expression
49Genes
50Genetic engineering
51hPBMCs
52hPBMCs, human peripheral blood mononuclear cells
53HPV
54HPV, human papillomavirus
55Human papillomavirus
56human peripheral blood mononuclear cells
57Humans
58IFN, interferon
59IGR, intergenic region
60IL, interleukin
61Immune response
62Immune response (humoral)
63Immune system
64Immunity
65Immunity, Innate - physiology
66inducible gene
67Influenza
68Innate immunity
69Interferon
70intergenic region
71interleukin
72Internal ribosome entry site
73internal ribosome entry sites
74Internal Ribosome Entry Sites - genetics
75IRES
76IRESs
77IRESs, internal ribosome entry sites
78L1 protein
79Laboratory animals
80Leukocytes
81Leukocytes (mononuclear)
82Leukocytes, Mononuclear - metabolism
83like particle
84like receptor
85linked immunosorbent assay
86linked immunospot
87Lymphocytes
88Lymphocytes T
89MERS
90MERS, Middle East respiratory syndrome
91Mice
92Mice, Inbred BALB C
93Mice, Inbred C57BL
94Middle East respiratory syndrome
95Myd88
96Myd88, myeloid differentiation primary response 88
97myeloid differentiation primary response 88
98NAbs
99NAbs, neutralizing antibodies
100neutralizing antibodies
101Papillomavirus infections
102Paralysis
103Peripheral blood mononuclear cells
104PFUs
105PFUs, plaque-forming units
106plaque
107PRNT, plaque-reduction neutralization test
108Proteins
109Recombinant proteins
110reduction neutralization test
111Respiratory diseases
112retinoic acid
113Ribonucleic acid
114RIG, retinoic acid-inducible gene
115RNA
116RNA - metabolism
117single
118Spike protein
119ssRNAs
120ssRNAs, single-stranded RNAs
121str
122T cells
123T helper 2
124T-Lymphocytes - metabolism
125Tfh
126Tfh, follicular helper T
127Tg, transgenic
128Th1
129Th1 Cells - metabolism
130Th1/Th2
131Th2
132Th2 Cells - metabolism
133Th2, T helper 2
134TLR, Toll-like receptor
135TLR7 protein
136TNF, tumor necrosis factor
137Toll
138Toll-like receptors
139transgenic
140tumor necrosis factor
141type
142Vaccine
143Vaccine efficacy
144Vaccines
145Vector-borne diseases
146virus
147Virus-like particles
148Viruses
149VLP, virus-like particle
150wild
151WT, wild-type
152Yellow fever
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Kwak, Hye Won
1Park, Hyo-Jung
2Ko, Hae Li
3Park, Hyelim
4Cha, Min Ho
5Lee, Sang-Myeong
6Kang, Kyung Won
7Kim, Rhoon-Ho
8Ryu, Seung Rok
9Kim, Hye-Jung
10Kim, Jae-Ouk
11Song, Manki
12Kim, Hun
13Jeong, Dae Gwin
14Shin, Eui-Cheol
15Nam, Jae-Hwan
collection
0Medline
1MEDLINE
2MEDLINE (Ovid)
3MEDLINE
4MEDLINE
5PubMed
6CrossRef
7Academic OneFile (A&I only)
8ProQuest Central (Corporate)
9Bacteriology Abstracts (Microbiology B)
10Nursing & Allied Health Database
11Health and Safety Science Abstracts (Full archive)
12Immunology Abstracts
13Virology and AIDS Abstracts
14Health & Medical Collection
15ProQuest Central (purchase pre-March 2016)
16Healthcare Administration Database (Alumni)
17Medical Database (Alumni Edition)
18ProQuest Pharma Collection
19Public Health Database
20ProQuest SciTech Collection
21ProQuest Natural Science Collection
22Hospital Premium Collection
23Hospital Premium Collection (Alumni Edition)
24ProQuest Central (Alumni) (purchase pre-March 2016)
25Research Library (Alumni Edition)
26ProQuest Central (Alumni Edition)
27ProQuest Central Essentials
28Biological Science Collection
29ProQuest Central
30Natural Science Collection
31Environmental Sciences and Pollution Management
32ProQuest Central Korea
33Health Research Premium Collection
34Health Research Premium Collection (Alumni)
35ProQuest Central Student
36Research Library Prep
37AIDS and Cancer Research Abstracts
38SciTech Premium Collection
39Consumer Health Database (Alumni Edition)
40ProQuest Health & Medical Complete (Alumni)
41Nursing & Allied Health Database (Alumni Edition)
42ProQuest Biological Science Collection
43Consumer Health Database
44Health & Medical Collection (Alumni Edition)
45Healthcare Administration Database
46Medical Database
47Research Library
48Algology Mycology and Protozoology Abstracts (Microbiology C)
49Biological Science Database
50Research Library (Corporate)
51Nursing & Allied Health Premium
52ProQuest One Academic Eastern Edition
53ProQuest One Academic
54ProQuest One Academic UKI Edition
55ProQuest Central Basic
56MEDLINE - Academic
57OpenAIRE (Open Access)
58OpenAIRE
59PubMed Central (Full Participant titles)
jtitleVaccine
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Kwak, Hye Won
1Park, Hyo-Jung
2Ko, Hae Li
3Park, Hyelim
4Cha, Min Ho
5Lee, Sang-Myeong
6Kang, Kyung Won
7Kim, Rhoon-Ho
8Ryu, Seung Rok
9Kim, Hye-Jung
10Kim, Jae-Ouk
11Song, Manki
12Kim, Hun
13Jeong, Dae Gwin
14Shin, Eui-Cheol
15Nam, Jae-Hwan
formatjournal
genrearticle
ristypeJOUR
atitleCricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response
jtitleVaccine
addtitleVaccine
date2019-08-23
risdate2019
volume37
issue36
spage5191
epage5202
pages5191-5202
issn0264-410X
eissn1873-2518
notesThese authors contributed equally to this work.
abstract•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.
copNetherlands
pubElsevier Ltd
pmid31371226
doi10.1016/j.vaccine.2019.07.070
orcidid
0https://orcid.org/0000-0001-7555-1091
1https://orcid.org/0000-0002-3624-3392
oafree_for_read