Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys
The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated in vivo delivery of these...
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| Veröffentlicht in: | Gene therapy 2017-08, Vol.24 (8), p.487-492 |
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| creator | Bischof, G F Shin, Y C Fuchs, S P Martinez-Navio, J M Lauer, W A Rakasz, E G Desrosiers, R C |
| description | The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated
in vivo
delivery of these antibodies in rhesus monkeys with previous studies that utilized intramuscular delivery with an adeno-associated virus (AAV) vector. Recombinant RRV-4L6 and RRV-5L7 were both shown to stably produce the antibodies in persistently infected B-cell lines in culture. Two RRV-negative rhesus monkeys were experimentally infected with recombinant RRV-4L6 and two with recombinant RRV-5L7. Following infection, the appearance of the delivered antibody was readily detected in all four animals. However, the levels of the delivered antibody were considerably lower than what has been typically observed following intramuscular AAV delivery. Furthermore, three of the four monkeys had an antibody response to the delivered antibody as had been observed previously with intramuscular AAV delivery of these same antibodies. We conclude that this recombinant herpesvirus has no inherent advantage over AAV for delivery of potentially therapeutic monoclonal antibodies in a rhesus monkey model. |
| doi_str_mv | 10.1038/gt.2017.49 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6258056</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A500801135</galeid><sourcerecordid>A500801135</sourcerecordid><originalsourceid>FETCH-LOGICAL-c561t-d3ed0637ce2c875cb2a79ddc506960ba17972133690bfb1e182d5cea354b34c93</originalsourceid><addsrcrecordid>eNp9kluL1DAUx4so7rj64geQgiBe6Jh7kxdhWbwsLCjqPoc0Pe1kbZvZJB3cb2-GWYcZFUkgcM7v_E_OpSieYrTEiMq3fVoShOslU_eKBWa1qDgT5H6xQEqoqsZEnhSPYrxGCLFakofFCZFCICnlovhyFaH0XWnK3oyjqUi5grCGuHFhjqXJt9yATT6UyZctDG4DoTRTco1vHcStNawgZnb00w-4jY-LB50ZIjy5e0-Lqw_vv59_qi4_f7w4P7usLBc4VS2FFglaWyBW1tw2xNSqbS1HQgnUGFyrmmBKhUJN12DAkrTcgqGcNZRZRU-Ldzvd9dyM0FqYUjCDXgc3mnCrvXH62DO5le79RgvCJeIiC7y8Ewj-ZoaY9OiihWEwE_g5aqwwk0zWimb0-R_otZ_DlMvTRGDOKaao_h-FFVGMcZ4r2lO9GUC7qfP5d3abWp9xhCTCmPJMLf9B5dPC6KyfoHPZfhTw6iggMwl-pt7MMeqLb1-P2RcH7ArMkFbRD3NyforH4OsdaIOPMUC3by9Gert6uk96u3qabQfy7HAge_T3rmXgzQ6I2TX1EA7687fcL3Mq3bo</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1929445521</pqid></control><display><type>article</type><title>Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Bischof, G F ; Shin, Y C ; Fuchs, S P ; Martinez-Navio, J M ; Lauer, W A ; Rakasz, E G ; Desrosiers, R C</creator><creatorcontrib>Bischof, G F ; Shin, Y C ; Fuchs, S P ; Martinez-Navio, J M ; Lauer, W A ; Rakasz, E G ; Desrosiers, R C</creatorcontrib><description>The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated
in vivo
delivery of these antibodies in rhesus monkeys with previous studies that utilized intramuscular delivery with an adeno-associated virus (AAV) vector. Recombinant RRV-4L6 and RRV-5L7 were both shown to stably produce the antibodies in persistently infected B-cell lines in culture. Two RRV-negative rhesus monkeys were experimentally infected with recombinant RRV-4L6 and two with recombinant RRV-5L7. Following infection, the appearance of the delivered antibody was readily detected in all four animals. However, the levels of the delivered antibody were considerably lower than what has been typically observed following intramuscular AAV delivery. Furthermore, three of the four monkeys had an antibody response to the delivered antibody as had been observed previously with intramuscular AAV delivery of these same antibodies. We conclude that this recombinant herpesvirus has no inherent advantage over AAV for delivery of potentially therapeutic monoclonal antibodies in a rhesus monkey model.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/gt.2017.49</identifier><identifier>PMID: 28660888</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/106 ; 13/44 ; 38 ; 38/1 ; 42 ; 42/44 ; 631/1647/2300/1514 ; 631/326/596 ; 64 ; Animals ; Antibodies, Monoclonal - genetics ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - metabolism ; Antibody response ; Biomedical and Life Sciences ; Biomedicine ; Care and treatment ; Cell Biology ; Cell culture ; Cell Line ; Cell lines ; Cells, Cultured ; Comparative analysis ; Dosage and administration ; Gene Expression ; Gene Therapy ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; Genetic Vectors - adverse effects ; Health aspects ; Herpes viruses ; Herpesvirus infections ; Human Genetics ; Immunoglobulins ; Infections ; Lymphocytes B ; Macaca mulatta ; Monkeys ; Monkeys & apes ; Monoclonal antibodies ; Nanotechnology ; Rhadinovirus - genetics ; Rhesus monkey ; short-communication ; Simian Immunodeficiency Virus - immunology ; Viruses</subject><ispartof>Gene therapy, 2017-08, Vol.24 (8), p.487-492</ispartof><rights>Macmillan Publishers Limited, part of Springer Nature. 2017</rights><rights>COPYRIGHT 2017 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2017</rights><rights>Macmillan Publishers Limited, part of Springer Nature. 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c561t-d3ed0637ce2c875cb2a79ddc506960ba17972133690bfb1e182d5cea354b34c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28660888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bischof, G F</creatorcontrib><creatorcontrib>Shin, Y C</creatorcontrib><creatorcontrib>Fuchs, S P</creatorcontrib><creatorcontrib>Martinez-Navio, J M</creatorcontrib><creatorcontrib>Lauer, W A</creatorcontrib><creatorcontrib>Rakasz, E G</creatorcontrib><creatorcontrib>Desrosiers, R C</creatorcontrib><title>Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated
in vivo
delivery of these antibodies in rhesus monkeys with previous studies that utilized intramuscular delivery with an adeno-associated virus (AAV) vector. Recombinant RRV-4L6 and RRV-5L7 were both shown to stably produce the antibodies in persistently infected B-cell lines in culture. Two RRV-negative rhesus monkeys were experimentally infected with recombinant RRV-4L6 and two with recombinant RRV-5L7. Following infection, the appearance of the delivered antibody was readily detected in all four animals. However, the levels of the delivered antibody were considerably lower than what has been typically observed following intramuscular AAV delivery. Furthermore, three of the four monkeys had an antibody response to the delivered antibody as had been observed previously with intramuscular AAV delivery of these same antibodies. We conclude that this recombinant herpesvirus has no inherent advantage over AAV for delivery of potentially therapeutic monoclonal antibodies in a rhesus monkey model.</description><subject>13/1</subject><subject>13/106</subject><subject>13/44</subject><subject>38</subject><subject>38/1</subject><subject>42</subject><subject>42/44</subject><subject>631/1647/2300/1514</subject><subject>631/326/596</subject><subject>64</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - genetics</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Antibody response</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cells, Cultured</subject><subject>Comparative analysis</subject><subject>Dosage and administration</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Genetic Therapy - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bischof, G F</au><au>Shin, Y C</au><au>Fuchs, S P</au><au>Martinez-Navio, J M</au><au>Lauer, W A</au><au>Rakasz, E G</au><au>Desrosiers, R C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys</atitle><jtitle>Gene therapy</jtitle><stitle>Gene Ther</stitle><addtitle>Gene Ther</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>24</volume><issue>8</issue><spage>487</spage><epage>492</epage><pages>487-492</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated
in vivo
delivery of these antibodies in rhesus monkeys with previous studies that utilized intramuscular delivery with an adeno-associated virus (AAV) vector. Recombinant RRV-4L6 and RRV-5L7 were both shown to stably produce the antibodies in persistently infected B-cell lines in culture. Two RRV-negative rhesus monkeys were experimentally infected with recombinant RRV-4L6 and two with recombinant RRV-5L7. Following infection, the appearance of the delivered antibody was readily detected in all four animals. However, the levels of the delivered antibody were considerably lower than what has been typically observed following intramuscular AAV delivery. Furthermore, three of the four monkeys had an antibody response to the delivered antibody as had been observed previously with intramuscular AAV delivery of these same antibodies. We conclude that this recombinant herpesvirus has no inherent advantage over AAV for delivery of potentially therapeutic monoclonal antibodies in a rhesus monkey model.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28660888</pmid><doi>10.1038/gt.2017.49</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Gene therapy, 2017-08, Vol.24 (8), p.487-492 |
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| subjects | 13/1 13/106 13/44 38 38/1 42 42/44 631/1647/2300/1514 631/326/596 64 Animals Antibodies, Monoclonal - genetics Antibodies, Monoclonal - immunology Antibodies, Monoclonal - metabolism Antibody response Biomedical and Life Sciences Biomedicine Care and treatment Cell Biology Cell culture Cell Line Cell lines Cells, Cultured Comparative analysis Dosage and administration Gene Expression Gene Therapy Genetic Therapy - methods Genetic Vectors - administration & dosage Genetic Vectors - adverse effects Health aspects Herpes viruses Herpesvirus infections Human Genetics Immunoglobulins Infections Lymphocytes B Macaca mulatta Monkeys Monkeys & apes Monoclonal antibodies Nanotechnology Rhadinovirus - genetics Rhesus monkey short-communication Simian Immunodeficiency Virus - immunology Viruses |
| title | Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys |
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