Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response.
Identifieur interne : 002293 ( Ncbi/Merge ); précédent : 002292; suivant : 002294Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response.
Auteurs : Hye Won Kwak [Corée du Sud] ; Hyo-Jung Park [Corée du Sud] ; Hae Li Ko [Corée du Sud] ; Hyelim Park [Corée du Sud] ; Min Ho Cha [Corée du Sud] ; Sang-Myeong Lee [Corée du Sud] ; Kyung Won Kang [Corée du Sud] ; Rhoon-Ho Kim [Corée du Sud] ; Seung Rok Ryu [Corée du Sud] ; Hye-Jung Kim [Corée du Sud] ; Jae-Ouk Kim [Corée du Sud] ; Manki Song [Corée du Sud] ; Hun Kim [Corée du Sud] ; Dae Gwin Jeong [Corée du Sud] ; Eui-Cheol Shin [Corée du Sud] ; Jae-Hwan Nam [Corée du Sud]Source :
- Vaccine [ 1873-2518 ] ; 2019.
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.
DOI: 10.1016/j.vaccine.2019.07.070
PubMed: 31371226
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Bucheon, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology, The Catholic University of Korea, Bucheon</wicri:regionArea><wicri:noRegion>Bucheon</wicri:noRegion></affiliation></author><author><name sortKey="Ko, Hae Li" sort="Ko, Hae Li" uniqKey="Ko H" first="Hae Li" last="Ko">Hae Li Ko</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology, The Catholic University of Korea, Bucheon</wicri:regionArea><wicri:noRegion>Bucheon</wicri:noRegion></affiliation></author><author><name sortKey="Park, Hyelim" sort="Park, Hyelim" uniqKey="Park H" first="Hyelim" last="Park">Hyelim Park</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology, The Catholic University of Korea, Bucheon</wicri:regionArea><wicri:noRegion>Bucheon</wicri:noRegion></affiliation></author><author><name sortKey="Cha, Min Ho" sort="Cha, Min Ho" uniqKey="Cha M" first="Min Ho" last="Cha">Min Ho Cha</name><affiliation wicri:level="1"><nlm:affiliation>KM Application Center, Korea Institute of Oriental Medicine, Daegu, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>KM Application Center, Korea Institute of Oriental Medicine, Daegu</wicri:regionArea><wicri:noRegion>Daegu</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Sang Myeong" sort="Lee, Sang Myeong" uniqKey="Lee S" first="Sang-Myeong" last="Lee">Sang-Myeong Lee</name><affiliation wicri:level="1"><nlm:affiliation>Division of Biotechnology, The Chonbuk National University, Iksan, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Biotechnology, The Chonbuk National University, Iksan</wicri:regionArea><wicri:noRegion>Iksan</wicri:noRegion></affiliation></author><author><name sortKey="Kang, Kyung Won" sort="Kang, Kyung Won" uniqKey="Kang K" first="Kyung Won" last="Kang">Kyung Won Kang</name><affiliation wicri:level="1"><nlm:affiliation>Division of Biotechnology, The Chonbuk National University, Iksan, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Biotechnology, The Chonbuk National University, Iksan</wicri:regionArea><wicri:noRegion>Iksan</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Rhoon Ho" sort="Kim, Rhoon Ho" uniqKey="Kim R" first="Rhoon-Ho" last="Kim">Rhoon-Ho Kim</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology, The Catholic University of Korea, Bucheon</wicri:regionArea><wicri:noRegion>Bucheon</wicri:noRegion></affiliation></author><author><name sortKey="Ryu, Seung Rok" sort="Ryu, Seung Rok" uniqKey="Ryu S" first="Seung Rok" last="Ryu">Seung Rok Ryu</name><affiliation wicri:level="1"><nlm:affiliation>Division of Biotechnology, The Chonbuk National University, Iksan, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Biotechnology, The Chonbuk National University, Iksan</wicri:regionArea><wicri:noRegion>Iksan</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Hye Jung" sort="Kim, Hye Jung" uniqKey="Kim H" first="Hye-Jung" last="Kim">Hye-Jung Kim</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology, The Catholic University of Korea, Bucheon</wicri:regionArea><wicri:noRegion>Bucheon</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Jae Ouk" sort="Kim, Jae Ouk" uniqKey="Kim J" first="Jae-Ouk" last="Kim">Jae-Ouk Kim</name><affiliation wicri:level="3"><nlm:affiliation>Clinical Research Lab, International Vaccine Institute, Seoul National University Research Park, Seoul, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Clinical Research Lab, International Vaccine Institute, Seoul National University Research Park, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Song, Manki" sort="Song, Manki" uniqKey="Song M" first="Manki" last="Song">Manki Song</name><affiliation wicri:level="3"><nlm:affiliation>Clinical Research Lab, International Vaccine Institute, Seoul National University Research Park, Seoul, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Clinical Research Lab, International Vaccine Institute, Seoul National University Research Park, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Hun" sort="Kim, Hun" uniqKey="Kim H" first="Hun" last="Kim">Hun Kim</name><affiliation wicri:level="1"><nlm:affiliation>Life Science Research Institute, SK Bioscience, Seongnam, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Life Science Research Institute, SK Bioscience, Seongnam</wicri:regionArea><wicri:noRegion>Seongnam</wicri:noRegion></affiliation></author><author><name sortKey="Jeong, Dae Gwin" sort="Jeong, Dae Gwin" uniqKey="Jeong D" first="Dae Gwin" last="Jeong">Dae Gwin Jeong</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Infectious Diseases Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Shin, Eui Cheol" sort="Shin, Eui Cheol" uniqKey="Shin E" first="Eui-Cheol" last="Shin">Eui-Cheol Shin</name><affiliation wicri:level="1"><nlm:affiliation>Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Nam, Jae Hwan" sort="Nam, Jae Hwan" uniqKey="Nam J" first="Jae-Hwan" last="Nam">Jae-Hwan Nam</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea. Electronic address: jhnam@catholic.ac.kr.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology, The Catholic University of Korea, Bucheon</wicri:regionArea><wicri:noRegion>Bucheon</wicri:noRegion></affiliation></author></analytic><series><title level="j">Vaccine</title><idno type="eISSN">1873-2518</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31371226</PMID><DateRevised><Year>2020</Year><Month>04</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-2518</ISSN><JournalIssue CitedMedium="Internet"><Volume>37</Volume><Issue>36</Issue><PubDate><Year>2019</Year><Month>Aug</Month><Day>23</Day></PubDate></JournalIssue><Title>Vaccine</Title><ISOAbbreviation>Vaccine</ISOAbbreviation></Journal><ArticleTitle>Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response.</ArticleTitle><Pagination><MedlinePgn>5191-5202</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0264-410X(19)30991-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.vaccine.2019.07.070</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>Copyright © 2019 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kwak</LastName><ForeName>Hye Won</ForeName><Initials>HW</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Hyo-Jung</ForeName><Initials>HJ</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ko</LastName><ForeName>Hae Li</ForeName><Initials>HL</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Hyelim</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cha</LastName><ForeName>Min Ho</ForeName><Initials>MH</Initials><AffiliationInfo><Affiliation>KM Application Center, Korea Institute of Oriental Medicine, Daegu, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Sang-Myeong</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Division of Biotechnology, The Chonbuk National University, Iksan, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kang</LastName><ForeName>Kyung Won</ForeName><Initials>KW</Initials><AffiliationInfo><Affiliation>Division of Biotechnology, The Chonbuk National University, Iksan, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Rhoon-Ho</ForeName><Initials>RH</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ryu</LastName><ForeName>Seung Rok</ForeName><Initials>SR</Initials><AffiliationInfo><Affiliation>Division of Biotechnology, The Chonbuk National University, Iksan, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Hye-Jung</ForeName><Initials>HJ</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Jae-Ouk</ForeName><Initials>JO</Initials><AffiliationInfo><Affiliation>Clinical Research Lab, International Vaccine Institute, Seoul National University Research Park, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Song</LastName><ForeName>Manki</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Clinical Research Lab, International Vaccine Institute, Seoul National University Research Park, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Hun</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Life Science Research Institute, SK Bioscience, Seongnam, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jeong</LastName><ForeName>Dae Gwin</ForeName><Initials>DG</Initials><AffiliationInfo><Affiliation>Infectious Diseases Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shin</LastName><ForeName>Eui-Cheol</ForeName><Initials>EC</Initials><AffiliationInfo><Affiliation>Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nam</LastName><ForeName>Jae-Hwan</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea. Electronic address: jhnam@catholic.ac.kr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Vaccine</MedlineTA><NlmUniqueID>8406899</NlmUniqueID><ISSNLinking>0264-410X</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Adjuvant</Keyword><Keyword MajorTopicYN="N">Alum</Keyword><Keyword MajorTopicYN="N">CrPV</Keyword><Keyword MajorTopicYN="N">HPV</Keyword><Keyword MajorTopicYN="N">IRES</Keyword><Keyword MajorTopicYN="N">MERS</Keyword><Keyword MajorTopicYN="N">RNA</Keyword><Keyword MajorTopicYN="N">Th1/Th2</Keyword><Keyword MajorTopicYN="N">Vaccine</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>05</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>06</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>07</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>8</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>8</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>8</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31371226</ArticleId><ArticleId IdType="pii">S0264-410X(19)30991-0</ArticleId><ArticleId IdType="doi">10.1016/j.vaccine.2019.07.070</ArticleId><ArticleId 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