A small antigenic determinant of the Chikungunya virus E2 protein is sufficient to induce neutralizing antibodies which are partially protective in mice
The mosquito-borne Chikungunya virus (CHIKV) causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so f...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2015-04, Vol.9 (4), p.e0003684-e0003684 |
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| description | The mosquito-borne Chikungunya virus (CHIKV) causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses.
E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L) and surface-exposed parts of the E2 domain A (sA) alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+) was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+) induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA), MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice.
The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine. |
| doi_str_mv | 10.1371/journal.pntd.0003684 |
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E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L) and surface-exposed parts of the E2 domain A (sA) alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+) was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+) induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA), MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice.
The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0003684</identifier><identifier>PMID: 25905779</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies, Neutralizing - blood ; Antibodies, Viral - blood ; Antigen-antibody reactions ; Chikungunya Fever - blood ; Chikungunya Fever - immunology ; Chikungunya virus ; Chikungunya virus - immunology ; Chikungunya virus - metabolism ; Climate change ; Epitopes - immunology ; Female ; Fever ; Genetic aspects ; Humans ; Infections ; Mice ; Mice, Inbred BALB C ; Mosquitoes ; Pain ; Properties ; Proteins ; Standard deviation ; Sulfuric acid ; Vaccines ; Viral Envelope Proteins - genetics ; Viral Envelope Proteins - immunology ; Viral Envelope Proteins - metabolism ; Viral proteins</subject><ispartof>PLoS neglected tropical diseases, 2015-04, Vol.9 (4), p.e0003684-e0003684</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Weber et al 2015 Weber et al</rights><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Weber C, Büchner SM, Schnierle BS (2015) A Small Antigenic Determinant of the Chikungunya Virus E2 Protein Is Sufficient to Induce Neutralizing Antibodies which Are Partially Protective in Mice. PLoS Negl Trop Dis 9(4): e0003684. doi:10.1371/journal.pntd.0003684</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c629t-85af10e33b89385f9c96b664b0bf15594e36b2fbf436f13a60de8d2855514bbe3</citedby><cites>FETCH-LOGICAL-c629t-85af10e33b89385f9c96b664b0bf15594e36b2fbf436f13a60de8d2855514bbe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407984/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407984/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25905779$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Williams, Maya</contributor><creatorcontrib>Weber, Christopher</creatorcontrib><creatorcontrib>Büchner, Sarah M</creatorcontrib><creatorcontrib>Schnierle, Barbara S</creatorcontrib><title>A small antigenic determinant of the Chikungunya virus E2 protein is sufficient to induce neutralizing antibodies which are partially protective in mice</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>The mosquito-borne Chikungunya virus (CHIKV) causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses.
E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L) and surface-exposed parts of the E2 domain A (sA) alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+) was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+) induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA), MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice.
The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine.</description><subject>Animals</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Antibodies, Viral - blood</subject><subject>Antigen-antibody reactions</subject><subject>Chikungunya Fever - blood</subject><subject>Chikungunya Fever - immunology</subject><subject>Chikungunya virus</subject><subject>Chikungunya virus - immunology</subject><subject>Chikungunya virus - metabolism</subject><subject>Climate change</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>Fever</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Infections</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mosquitoes</subject><subject>Pain</subject><subject>Properties</subject><subject>Proteins</subject><subject>Standard deviation</subject><subject>Sulfuric acid</subject><subject>Vaccines</subject><subject>Viral Envelope Proteins - genetics</subject><subject>Viral Envelope Proteins - immunology</subject><subject>Viral Envelope Proteins - metabolism</subject><subject>Viral proteins</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqNUt2OEyEYnRiNu1bfwCiJifGmFYZhBm42aZpVN9nEG70mDPPRoU6hAlNTn8THlf7spk28EC4gH-ecDw6nKF4TPCO0IR9XfgxODbONS90MY0xrXj0promgbFo2lD09218VL2JcYcwE4-R5cVUygVnTiOvizxzFtRoGpFyyS3BWow4ShLV1uYK8QakHtOjtj9EtR7dTaGvDGNFtiTbBJ7AO2YjiaIzVFjIjeWRdN2pADsYU1GB_W7c8yLe-sxDRr97qHqkAaKNCsrn57qilk91CZqO11fCyeGbUEOHVaZ0U3z_dflt8md5__Xy3mN9PdV2KNOVMGYKB0pYLypkRWtRtXVctbg1hTFRA67Y0ralobQhVNe6AdyVnjJGqbYFOirdH3c3gozyZGiWpOasp42WdEXdHROfVSm6CXauwk15ZeSj4sJT7d-gBJCNNq6nmgrRlpYURleIC47JjzCgs9lo3p25ju4ZOZ8eyRReilyfO9nLpt7KqcCN4lQU-nASC_zlCTHJto4ZhUA78eLh3U_MyJ-Q_oA3jDaN5TIp3R-hS5VdYZ3xurvdwOa8IF9kGvBec_QOVZwf5x7wDY3P9gvD-jNCDGlIf_TAm6128BFZHoA4-xgDm0RGC5T7tDx8j92mXp7Rn2ptzNx9JD_GmfwHVof64</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Weber, Christopher</creator><creator>Büchner, Sarah M</creator><creator>Schnierle, Barbara S</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7U9</scope><scope>C1K</scope><scope>F1W</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150401</creationdate><title>A small antigenic determinant of the Chikungunya virus E2 protein is sufficient to induce neutralizing antibodies which are partially protective in mice</title><author>Weber, Christopher ; Büchner, Sarah M ; Schnierle, Barbara S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c629t-85af10e33b89385f9c96b664b0bf15594e36b2fbf436f13a60de8d2855514bbe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antibodies, Neutralizing - blood</topic><topic>Antibodies, Viral - blood</topic><topic>Antigen-antibody reactions</topic><topic>Chikungunya Fever - blood</topic><topic>Chikungunya Fever - immunology</topic><topic>Chikungunya virus</topic><topic>Chikungunya virus - immunology</topic><topic>Chikungunya virus - metabolism</topic><topic>Climate change</topic><topic>Epitopes - immunology</topic><topic>Female</topic><topic>Fever</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Infections</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mosquitoes</topic><topic>Pain</topic><topic>Properties</topic><topic>Proteins</topic><topic>Standard deviation</topic><topic>Sulfuric acid</topic><topic>Vaccines</topic><topic>Viral Envelope Proteins - genetics</topic><topic>Viral Envelope Proteins - immunology</topic><topic>Viral Envelope Proteins - metabolism</topic><topic>Viral proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Weber, Christopher</creatorcontrib><creatorcontrib>Büchner, Sarah M</creatorcontrib><creatorcontrib>Schnierle, Barbara S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weber, Christopher</au><au>Büchner, Sarah M</au><au>Schnierle, Barbara S</au><au>Williams, Maya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A small antigenic determinant of the Chikungunya virus E2 protein is sufficient to induce neutralizing antibodies which are partially protective in mice</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>9</volume><issue>4</issue><spage>e0003684</spage><epage>e0003684</epage><pages>e0003684-e0003684</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>The mosquito-borne Chikungunya virus (CHIKV) causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses.
E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L) and surface-exposed parts of the E2 domain A (sA) alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+) was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+) induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA), MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice.
The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25905779</pmid><doi>10.1371/journal.pntd.0003684</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies, Neutralizing - blood Antibodies, Viral - blood Antigen-antibody reactions Chikungunya Fever - blood Chikungunya Fever - immunology Chikungunya virus Chikungunya virus - immunology Chikungunya virus - metabolism Climate change Epitopes - immunology Female Fever Genetic aspects Humans Infections Mice Mice, Inbred BALB C Mosquitoes Pain Properties Proteins Standard deviation Sulfuric acid Vaccines Viral Envelope Proteins - genetics Viral Envelope Proteins - immunology Viral Envelope Proteins - metabolism Viral proteins |
| title | A small antigenic determinant of the Chikungunya virus E2 protein is sufficient to induce neutralizing antibodies which are partially protective in mice |
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