Combinations of 3-Hydroxyphthalic Anhydride-Modified Ovalbumin With Antiretroviral Drug-Based Microbicide Candidates Display Synergistic and Complementary Effects Against HIV-1 Infection
BACKGROUND:The development of a safe, effective, and affordable microbicide to prevent the sexual transmission of HIV combination is urgently needed. Our previous studies demonstrated that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibited potent antiviral activity against a b...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2011-04, Vol.56 (5), p.384-392 |
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| container_title | Journal of acquired immune deficiency syndromes (1999) |
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| creator | Li, Lin Tan, Suiyi Lu, Hong Lu, Lu Yang, Jie Jin, Hong Liu, Shuwen Jiang, Shibo |
| description | BACKGROUND:The development of a safe, effective, and affordable microbicide to prevent the sexual transmission of HIV combination is urgently needed. Our previous studies demonstrated that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibited potent antiviral activity against a broad spectrum of HIV, simian immunodeficiency virus, and herpes simplex virus, making it a promising candidate as a component of combination microbicide. We intended to evaluate potential the synergistic anti-HIV-1 effect of HP-OVA in combination with antiretroviral drug (ARV)-based microbicide candidates.
METHODS:The antiviral activity of HP-OVA and the ARVs, including HIV-1 entry inhibitors (T20, C52L, NB64, NBD556, AMD3100, and Maraviroc) and reverse transcriptase inhibitors (Tenofovir, UC781, and TMC120), tested alone or in combination, against HIV-1 X4 and R5 viruses, including some drug-resistant strains, was determined in MT-2 and peripheral blood mononuclear cells using p24 assay. The immune responses induced by HP-OVA that was applied in the vaginas of rats were detected by enzyme-linked immunosorbent assay.
RESULTS:When each of these ARV-based microbicide candidates was combined with HP-OVA, synergistic activity was observed against infection by both X4 and R5 strains, and the degree of synergy differed in each case. HP-OVA was highly effective against several ARV-resistant HIV-1 strains, suggesting that combining HP-OVA with these ARV-based microbicide candidates might work cooperatively against both drug-sensitive and -resistant HIV-1 strains. Human body fluids and human proteins had little or no effects on HP-OVA-mediated inhibitory activity against HIV-1 infection. HP-OVA formulated in the universal gel maintained its antiviral activity for at least 1 month and only induced weak immune responses after its multiple applications in the vaginas of rats.
CONCLUSIONS:Synergistic and complementary effects against infection by a broad spectrum of HIV-1 strains were observed by combining HP-OVA with the ARV-based microbicide candidates. These findings provide a sound scientific platform for the development of a safe, effective, and affordable combination microbicide to prevent the sexual transmission of HIV and other sexually transmissible viruses. |
| doi_str_mv | 10.1097/QAI.0b013e31820a4a8d |
| format | Article |
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METHODS:The antiviral activity of HP-OVA and the ARVs, including HIV-1 entry inhibitors (T20, C52L, NB64, NBD556, AMD3100, and Maraviroc) and reverse transcriptase inhibitors (Tenofovir, UC781, and TMC120), tested alone or in combination, against HIV-1 X4 and R5 viruses, including some drug-resistant strains, was determined in MT-2 and peripheral blood mononuclear cells using p24 assay. The immune responses induced by HP-OVA that was applied in the vaginas of rats were detected by enzyme-linked immunosorbent assay.
RESULTS:When each of these ARV-based microbicide candidates was combined with HP-OVA, synergistic activity was observed against infection by both X4 and R5 strains, and the degree of synergy differed in each case. HP-OVA was highly effective against several ARV-resistant HIV-1 strains, suggesting that combining HP-OVA with these ARV-based microbicide candidates might work cooperatively against both drug-sensitive and -resistant HIV-1 strains. Human body fluids and human proteins had little or no effects on HP-OVA-mediated inhibitory activity against HIV-1 infection. HP-OVA formulated in the universal gel maintained its antiviral activity for at least 1 month and only induced weak immune responses after its multiple applications in the vaginas of rats.
CONCLUSIONS:Synergistic and complementary effects against infection by a broad spectrum of HIV-1 strains were observed by combining HP-OVA with the ARV-based microbicide candidates. These findings provide a sound scientific platform for the development of a safe, effective, and affordable combination microbicide to prevent the sexual transmission of HIV and other sexually transmissible viruses.</description><identifier>ISSN: 1525-4135</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0b013e31820a4a8d</identifier><identifier>PMID: 21239999</identifier><identifier>CODEN: JDSRET</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>Animals ; Anti-HIV Agents - therapeutic use ; Antiretroviral drugs ; Biological and medical sciences ; Chickens ; Disease Transmission, Infectious - prevention & control ; Drug resistance ; Drug Synergism ; Drug Therapy, Combination ; Effects ; Female ; Fundamental and applied biological sciences. Psychology ; Herpes simplex virus ; Herpes viruses ; HIV ; HIV Fusion Inhibitors - therapeutic use ; HIV Infections - drug therapy ; HIV Infections - prevention & control ; HIV Infections - transmission ; HIV Infections - virology ; HIV-1 ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Human viral diseases ; Humans ; Infectious diseases ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - virology ; Medical sciences ; Microbiology ; Miscellaneous ; Ovalbumin - chemistry ; Ovalbumin - therapeutic use ; Phthalic Anhydrides - chemistry ; Rats ; Reverse Transcriptase Inhibitors - therapeutic use ; Rodents ; Sexually transmitted diseases ; Simian immunodeficiency virus ; STD ; Treatment Outcome ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Virology</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2011-04, Vol.56 (5), p.384-392</ispartof><rights>2011 Lippincott Williams & Wilkins, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Lippincott Williams & Wilkins Apr 15, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c545d-81f6c675ad60864140e25af719bd6cfce9c736266759e08a170d3a4357ed71ee3</citedby><cites>FETCH-LOGICAL-c545d-81f6c675ad60864140e25af719bd6cfce9c736266759e08a170d3a4357ed71ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24024467$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21239999$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Lin</creatorcontrib><creatorcontrib>Tan, Suiyi</creatorcontrib><creatorcontrib>Lu, Hong</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Yang, Jie</creatorcontrib><creatorcontrib>Jin, Hong</creatorcontrib><creatorcontrib>Liu, Shuwen</creatorcontrib><creatorcontrib>Jiang, Shibo</creatorcontrib><title>Combinations of 3-Hydroxyphthalic Anhydride-Modified Ovalbumin With Antiretroviral Drug-Based Microbicide Candidates Display Synergistic and Complementary Effects Against HIV-1 Infection</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>BACKGROUND:The development of a safe, effective, and affordable microbicide to prevent the sexual transmission of HIV combination is urgently needed. Our previous studies demonstrated that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibited potent antiviral activity against a broad spectrum of HIV, simian immunodeficiency virus, and herpes simplex virus, making it a promising candidate as a component of combination microbicide. We intended to evaluate potential the synergistic anti-HIV-1 effect of HP-OVA in combination with antiretroviral drug (ARV)-based microbicide candidates.
METHODS:The antiviral activity of HP-OVA and the ARVs, including HIV-1 entry inhibitors (T20, C52L, NB64, NBD556, AMD3100, and Maraviroc) and reverse transcriptase inhibitors (Tenofovir, UC781, and TMC120), tested alone or in combination, against HIV-1 X4 and R5 viruses, including some drug-resistant strains, was determined in MT-2 and peripheral blood mononuclear cells using p24 assay. The immune responses induced by HP-OVA that was applied in the vaginas of rats were detected by enzyme-linked immunosorbent assay.
RESULTS:When each of these ARV-based microbicide candidates was combined with HP-OVA, synergistic activity was observed against infection by both X4 and R5 strains, and the degree of synergy differed in each case. HP-OVA was highly effective against several ARV-resistant HIV-1 strains, suggesting that combining HP-OVA with these ARV-based microbicide candidates might work cooperatively against both drug-sensitive and -resistant HIV-1 strains. Human body fluids and human proteins had little or no effects on HP-OVA-mediated inhibitory activity against HIV-1 infection. HP-OVA formulated in the universal gel maintained its antiviral activity for at least 1 month and only induced weak immune responses after its multiple applications in the vaginas of rats.
CONCLUSIONS:Synergistic and complementary effects against infection by a broad spectrum of HIV-1 strains were observed by combining HP-OVA with the ARV-based microbicide candidates. These findings provide a sound scientific platform for the development of a safe, effective, and affordable combination microbicide to prevent the sexual transmission of HIV and other sexually transmissible viruses.</description><subject>Animals</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral drugs</subject><subject>Biological and medical sciences</subject><subject>Chickens</subject><subject>Disease Transmission, Infectious - prevention & control</subject><subject>Drug resistance</subject><subject>Drug Synergism</subject><subject>Drug Therapy, Combination</subject><subject>Effects</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Herpes simplex virus</subject><subject>Herpes viruses</subject><subject>HIV</subject><subject>HIV Fusion Inhibitors - therapeutic use</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - prevention & control</subject><subject>HIV Infections - transmission</subject><subject>HIV Infections - virology</subject><subject>HIV-1</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Leukocytes, Mononuclear - virology</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Ovalbumin - chemistry</subject><subject>Ovalbumin - therapeutic use</subject><subject>Phthalic Anhydrides - chemistry</subject><subject>Rats</subject><subject>Reverse Transcriptase Inhibitors - therapeutic use</subject><subject>Rodents</subject><subject>Sexually transmitted diseases</subject><subject>Simian immunodeficiency virus</subject><subject>STD</subject><subject>Treatment Outcome</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Virology</subject><issn>1525-4135</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kt9uFCEUxidGY2v1DYwhJsarqTAwDHNjsm6ru0mbxvjvkjDA7FBnYQtM676aT-dpdq3aC-ECcs7vHL5DvqJ4TvAxwW3z5uNseYw7TKilRFRYMSXMg-KQtIyVjRDsIdzrqi4ZofVB8SSlS4wJZ6x9XBxUpKItrMPi5zysO-dVdsEnFHpEy8XWxPBjuxnyoEan0cwPEHHGlufBuN5Zgy6u1dhNa-fRN5cHILKLNsdw7aIa0UmcVuU7lQA8dzqGzmmoRnPljTMq24ROXNqMaos-bb2NK5cyPANZBGI2o11bn1XcotO-tzonNFsp51NGi-XXkqClv42C3KfFo16NyT7bn0fFl_enn-eL8uziw3I-Oyt1zWpTCtJzzZtaGY4FZ4RhW9Wqb0jbGa57bVvdUF5xQFqLhSINNlQxWjfWNMRaelS83fXdTN3aGg3qYEq5iW4NKmVQTv6b8W6Qq3AtKRaMcg4NXu8bxHA12ZTl2iVtx1F5G6YkW8yYgE2BfHmPvAxT9DCdFBxjQQjHALEdBF-bUrT9nRSC5a01JFhD3rcGlL34e4y7ot9eAODVHlBJq7GPymuX_nAMV4zxBjix427CmG1M38fpxkY5WDXm4f8afgGHxdmC</recordid><startdate>20110415</startdate><enddate>20110415</enddate><creator>Li, Lin</creator><creator>Tan, Suiyi</creator><creator>Lu, Hong</creator><creator>Lu, Lu</creator><creator>Yang, Jie</creator><creator>Jin, Hong</creator><creator>Liu, Shuwen</creator><creator>Jiang, Shibo</creator><general>Lippincott Williams & Wilkins, Inc</general><general>Lippincott Williams & Wilkins</general><general>Lippincott Williams & Wilkins Ovid Technologies</general><scope>IQODW</scope><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>7T2</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>5PM</scope></search><sort><creationdate>20110415</creationdate><title>Combinations of 3-Hydroxyphthalic Anhydride-Modified Ovalbumin With Antiretroviral Drug-Based Microbicide Candidates Display Synergistic and Complementary Effects Against HIV-1 Infection</title><author>Li, Lin ; Tan, Suiyi ; Lu, Hong ; Lu, Lu ; Yang, Jie ; Jin, Hong ; Liu, Shuwen ; Jiang, Shibo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c545d-81f6c675ad60864140e25af719bd6cfce9c736266759e08a170d3a4357ed71ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antiretroviral drugs</topic><topic>Biological and medical sciences</topic><topic>Chickens</topic><topic>Disease Transmission, Infectious - prevention & control</topic><topic>Drug resistance</topic><topic>Drug Synergism</topic><topic>Drug Therapy, Combination</topic><topic>Effects</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Herpes simplex virus</topic><topic>Herpes viruses</topic><topic>HIV</topic><topic>HIV Fusion Inhibitors - therapeutic use</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - prevention & control</topic><topic>HIV Infections - transmission</topic><topic>HIV Infections - virology</topic><topic>HIV-1</topic><topic>Human immunodeficiency virus</topic><topic>Human immunodeficiency virus 1</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Leukocytes, Mononuclear - drug effects</topic><topic>Leukocytes, Mononuclear - virology</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Ovalbumin - chemistry</topic><topic>Ovalbumin - therapeutic use</topic><topic>Phthalic Anhydrides - chemistry</topic><topic>Rats</topic><topic>Reverse Transcriptase Inhibitors - therapeutic use</topic><topic>Rodents</topic><topic>Sexually transmitted diseases</topic><topic>Simian immunodeficiency virus</topic><topic>STD</topic><topic>Treatment Outcome</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Lin</creatorcontrib><creatorcontrib>Tan, Suiyi</creatorcontrib><creatorcontrib>Lu, Hong</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Yang, Jie</creatorcontrib><creatorcontrib>Jin, Hong</creatorcontrib><creatorcontrib>Liu, Shuwen</creatorcontrib><creatorcontrib>Jiang, Shibo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Lin</au><au>Tan, Suiyi</au><au>Lu, Hong</au><au>Lu, Lu</au><au>Yang, Jie</au><au>Jin, Hong</au><au>Liu, Shuwen</au><au>Jiang, Shibo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combinations of 3-Hydroxyphthalic Anhydride-Modified Ovalbumin With Antiretroviral Drug-Based Microbicide Candidates Display Synergistic and Complementary Effects Against HIV-1 Infection</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2011-04-15</date><risdate>2011</risdate><volume>56</volume><issue>5</issue><spage>384</spage><epage>392</epage><pages>384-392</pages><issn>1525-4135</issn><eissn>1944-7884</eissn><coden>JDSRET</coden><abstract>BACKGROUND:The development of a safe, effective, and affordable microbicide to prevent the sexual transmission of HIV combination is urgently needed. Our previous studies demonstrated that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibited potent antiviral activity against a broad spectrum of HIV, simian immunodeficiency virus, and herpes simplex virus, making it a promising candidate as a component of combination microbicide. We intended to evaluate potential the synergistic anti-HIV-1 effect of HP-OVA in combination with antiretroviral drug (ARV)-based microbicide candidates.
METHODS:The antiviral activity of HP-OVA and the ARVs, including HIV-1 entry inhibitors (T20, C52L, NB64, NBD556, AMD3100, and Maraviroc) and reverse transcriptase inhibitors (Tenofovir, UC781, and TMC120), tested alone or in combination, against HIV-1 X4 and R5 viruses, including some drug-resistant strains, was determined in MT-2 and peripheral blood mononuclear cells using p24 assay. The immune responses induced by HP-OVA that was applied in the vaginas of rats were detected by enzyme-linked immunosorbent assay.
RESULTS:When each of these ARV-based microbicide candidates was combined with HP-OVA, synergistic activity was observed against infection by both X4 and R5 strains, and the degree of synergy differed in each case. HP-OVA was highly effective against several ARV-resistant HIV-1 strains, suggesting that combining HP-OVA with these ARV-based microbicide candidates might work cooperatively against both drug-sensitive and -resistant HIV-1 strains. Human body fluids and human proteins had little or no effects on HP-OVA-mediated inhibitory activity against HIV-1 infection. HP-OVA formulated in the universal gel maintained its antiviral activity for at least 1 month and only induced weak immune responses after its multiple applications in the vaginas of rats.
CONCLUSIONS:Synergistic and complementary effects against infection by a broad spectrum of HIV-1 strains were observed by combining HP-OVA with the ARV-based microbicide candidates. These findings provide a sound scientific platform for the development of a safe, effective, and affordable combination microbicide to prevent the sexual transmission of HIV and other sexually transmissible viruses.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>21239999</pmid><doi>10.1097/QAI.0b013e31820a4a8d</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1525-4135 |
| ispartof | Journal of acquired immune deficiency syndromes (1999), 2011-04, Vol.56 (5), p.384-392 |
| issn | 1525-4135 1944-7884 |
| language | eng |
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| source | MEDLINE; Journals@Ovid LWW Legacy Archive; Journals@Ovid Complete; Free E- Journals |
| subjects | Animals Anti-HIV Agents - therapeutic use Antiretroviral drugs Biological and medical sciences Chickens Disease Transmission, Infectious - prevention & control Drug resistance Drug Synergism Drug Therapy, Combination Effects Female Fundamental and applied biological sciences. Psychology Herpes simplex virus Herpes viruses HIV HIV Fusion Inhibitors - therapeutic use HIV Infections - drug therapy HIV Infections - prevention & control HIV Infections - transmission HIV Infections - virology HIV-1 Human immunodeficiency virus Human immunodeficiency virus 1 Human viral diseases Humans Infectious diseases Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - virology Medical sciences Microbiology Miscellaneous Ovalbumin - chemistry Ovalbumin - therapeutic use Phthalic Anhydrides - chemistry Rats Reverse Transcriptase Inhibitors - therapeutic use Rodents Sexually transmitted diseases Simian immunodeficiency virus STD Treatment Outcome Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Virology |
| title | Combinations of 3-Hydroxyphthalic Anhydride-Modified Ovalbumin With Antiretroviral Drug-Based Microbicide Candidates Display Synergistic and Complementary Effects Against HIV-1 Infection |
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