A therapeutic HIV-1 vaccine reduces markers of systemic immune activation and latent infection in patients under highly active antiretroviral therapy
•Immune assays were performed on HIV-1 patients receiving therapeutic vaccine HIVAX.•HIVAX reduced the latent viral pool as measured by 2-LTR circles and total HIV-1 DNA.•HIVAX reduced serum cytokines and cellular markers of systemic immune activation.•HIVAX increased markers of activation on gag-sp...
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| Veröffentlicht in: | Vaccine 2020-06, Vol.38 (27), p.4336-4345 |
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| creator | Pallikkuth, Suresh Bolivar, Hector Fletcher, Mary A. Babic, Dunja Z. De Armas, Lesley R. Gupta, Sachin Termini, James M. Arheart, Kristopher L. Stevenson, Mario Tung, Frank Y. Fischl, Margaret A. Pahwa, Savita Stone, Geoffrey W |
| description | •Immune assays were performed on HIV-1 patients receiving therapeutic vaccine HIVAX.•HIVAX reduced the latent viral pool as measured by 2-LTR circles and total HIV-1 DNA.•HIVAX reduced serum cytokines and cellular markers of systemic immune activation.•HIVAX increased markers of activation on gag-specific CD4 + T cells.•HIVAX may suppress immune activation and latent infection in HIV-1 infected patients.
HIV infection is characterized by chronic immune activation and the establishment of a pool of latently infected cells. Antiretroviral therapy (ART) can suppress viral load to undetectable levels in peripheral blood by standard measure, however immune activation/chronic inflammation and latent infection persist and affect quality of life. We have now shown that a novel therapeutic HIV vaccine consisting of replication-defective HIV (HIVAX), given in the context of viral suppression under ART, can reduce both immune activation/chronic inflammation and latent infection. Immune activation, as measured by percent of CD8 + HLA-DR + CD38 + T cells, approached levels of healthy controls at week 16 following vaccination. Reduced immune activation was accompanied by a reduction in pro-inflammatory cytokines and peripheral α4β7 + plasmacytoid DC (a marker of mucosal immune activation). Levels of both HIV-1 DNA and 2-LTR circles were reduced at week 16 following vaccination, suggesting HIVAX can impact HIV-1 latency and reduce viral replication. Surprisingly, reduced immune activation/chronic inflammation was accompanied by an increase in the percent of memory CD4 + T cells expressing markers PD-1 and TIM-3. In addition, evaluation of HIV-1 Gag-specific CD4 + T cells for expression of 96 T cell related genes pre- and post-therapy revealed increased expression of a number of genes involved in the regulation of immune activation, T cell activation, and antiviral responses. Overall this study provides evidence that vaccination with HIVAX in subjects under long term antiviral suppression can reduce immune activation/chronic inflammation and latent infection (Clinicaltrials.gov, identifier NCT01428596). |
| doi_str_mv | 10.1016/j.vaccine.2020.04.015 |
| format | Article |
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HIV infection is characterized by chronic immune activation and the establishment of a pool of latently infected cells. Antiretroviral therapy (ART) can suppress viral load to undetectable levels in peripheral blood by standard measure, however immune activation/chronic inflammation and latent infection persist and affect quality of life. We have now shown that a novel therapeutic HIV vaccine consisting of replication-defective HIV (HIVAX), given in the context of viral suppression under ART, can reduce both immune activation/chronic inflammation and latent infection. Immune activation, as measured by percent of CD8 + HLA-DR + CD38 + T cells, approached levels of healthy controls at week 16 following vaccination. Reduced immune activation was accompanied by a reduction in pro-inflammatory cytokines and peripheral α4β7 + plasmacytoid DC (a marker of mucosal immune activation). Levels of both HIV-1 DNA and 2-LTR circles were reduced at week 16 following vaccination, suggesting HIVAX can impact HIV-1 latency and reduce viral replication. Surprisingly, reduced immune activation/chronic inflammation was accompanied by an increase in the percent of memory CD4 + T cells expressing markers PD-1 and TIM-3. In addition, evaluation of HIV-1 Gag-specific CD4 + T cells for expression of 96 T cell related genes pre- and post-therapy revealed increased expression of a number of genes involved in the regulation of immune activation, T cell activation, and antiviral responses. Overall this study provides evidence that vaccination with HIVAX in subjects under long term antiviral suppression can reduce immune activation/chronic inflammation and latent infection (Clinicaltrials.gov, identifier NCT01428596).</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2020.04.015</identifier><identifier>PMID: 32387010</identifier><language>eng</language><publisher>OXFORD: Elsevier Ltd</publisher><subject>Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral Therapy, Highly Active ; Biomarkers ; CD38 antigen ; CD4 antigen ; CD4-Positive T-Lymphocytes ; CD8 antigen ; CD8-Positive T-Lymphocytes ; Cell activation ; Chronic infection ; Cytokines ; Deoxyribonucleic acid ; DNA ; Drug therapy ; Flow cytometry ; Gag protein ; Gene expression ; Gene regulation ; Genes ; Highly active antiretroviral therapy ; Histocompatibility antigen HLA ; HIV ; HIV Infections - drug therapy ; HIV-1 ; Human immunodeficiency virus ; Humans ; Immune activation ; Immune responses ; Immunization ; Immunological memory ; Immunology ; Infections ; Inflammation ; Latency ; Latent Infection ; Latent viral infection ; Life Sciences & Biomedicine ; Lymphocyte Activation ; Lymphocytes ; Lymphocytes T ; Medicine, Research & Experimental ; Memory cells ; Mucosal immunity ; PD-1 protein ; Peripheral blood ; Plasma ; Proteins ; Quality of Life ; Replication ; Research & Experimental Medicine ; Science & Technology ; T-cell activation ; Therapeutic vaccine ; Therapy ; Vaccination ; Vaccines ; Viral Load</subject><ispartof>Vaccine, 2020-06, Vol.38 (27), p.4336-4345</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><rights>2020. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>4</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000534219400016</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c393t-84d449290043998bb6e62891bd5acc301b6df4ddbb90c638d996a6d75f04e3b23</citedby><cites>FETCH-LOGICAL-c393t-84d449290043998bb6e62891bd5acc301b6df4ddbb90c638d996a6d75f04e3b23</cites><orcidid>0000-0002-3212-1566 ; 0000-0002-4470-4216</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2425692088?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,28257,46004,64394,64396,64398,72478</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32387010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pallikkuth, Suresh</creatorcontrib><creatorcontrib>Bolivar, Hector</creatorcontrib><creatorcontrib>Fletcher, Mary A.</creatorcontrib><creatorcontrib>Babic, Dunja Z.</creatorcontrib><creatorcontrib>De Armas, Lesley R.</creatorcontrib><creatorcontrib>Gupta, Sachin</creatorcontrib><creatorcontrib>Termini, James M.</creatorcontrib><creatorcontrib>Arheart, Kristopher L.</creatorcontrib><creatorcontrib>Stevenson, Mario</creatorcontrib><creatorcontrib>Tung, Frank Y.</creatorcontrib><creatorcontrib>Fischl, Margaret A.</creatorcontrib><creatorcontrib>Pahwa, Savita</creatorcontrib><creatorcontrib>Stone, Geoffrey W</creatorcontrib><title>A therapeutic HIV-1 vaccine reduces markers of systemic immune activation and latent infection in patients under highly active antiretroviral therapy</title><title>Vaccine</title><addtitle>VACCINE</addtitle><addtitle>Vaccine</addtitle><description>•Immune assays were performed on HIV-1 patients receiving therapeutic vaccine HIVAX.•HIVAX reduced the latent viral pool as measured by 2-LTR circles and total HIV-1 DNA.•HIVAX reduced serum cytokines and cellular markers of systemic immune activation.•HIVAX increased markers of activation on gag-specific CD4 + T cells.•HIVAX may suppress immune activation and latent infection in HIV-1 infected patients.
HIV infection is characterized by chronic immune activation and the establishment of a pool of latently infected cells. Antiretroviral therapy (ART) can suppress viral load to undetectable levels in peripheral blood by standard measure, however immune activation/chronic inflammation and latent infection persist and affect quality of life. We have now shown that a novel therapeutic HIV vaccine consisting of replication-defective HIV (HIVAX), given in the context of viral suppression under ART, can reduce both immune activation/chronic inflammation and latent infection. Immune activation, as measured by percent of CD8 + HLA-DR + CD38 + T cells, approached levels of healthy controls at week 16 following vaccination. Reduced immune activation was accompanied by a reduction in pro-inflammatory cytokines and peripheral α4β7 + plasmacytoid DC (a marker of mucosal immune activation). Levels of both HIV-1 DNA and 2-LTR circles were reduced at week 16 following vaccination, suggesting HIVAX can impact HIV-1 latency and reduce viral replication. Surprisingly, reduced immune activation/chronic inflammation was accompanied by an increase in the percent of memory CD4 + T cells expressing markers PD-1 and TIM-3. In addition, evaluation of HIV-1 Gag-specific CD4 + T cells for expression of 96 T cell related genes pre- and post-therapy revealed increased expression of a number of genes involved in the regulation of immune activation, T cell activation, and antiviral responses. Overall this study provides evidence that vaccination with HIVAX in subjects under long term antiviral suppression can reduce immune activation/chronic inflammation and latent infection (Clinicaltrials.gov, identifier NCT01428596).</description><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Biomarkers</subject><subject>CD38 antigen</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Cell activation</subject><subject>Chronic infection</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Drug therapy</subject><subject>Flow cytometry</subject><subject>Gag protein</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Highly active antiretroviral therapy</subject><subject>Histocompatibility antigen HLA</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV-1</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immune activation</subject><subject>Immune responses</subject><subject>Immunization</subject><subject>Immunological memory</subject><subject>Immunology</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Latency</subject><subject>Latent Infection</subject><subject>Latent viral infection</subject><subject>Life Sciences & Biomedicine</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine, Research & Experimental</subject><subject>Memory cells</subject><subject>Mucosal immunity</subject><subject>PD-1 protein</subject><subject>Peripheral blood</subject><subject>Plasma</subject><subject>Proteins</subject><subject>Quality of Life</subject><subject>Replication</subject><subject>Research & Experimental Medicine</subject><subject>Science & Technology</subject><subject>T-cell activation</subject><subject>Therapeutic vaccine</subject><subject>Therapy</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Viral 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therapeutic HIV-1 vaccine reduces markers of systemic immune activation and latent infection in patients under highly active antiretroviral therapy</title><author>Pallikkuth, Suresh ; Bolivar, Hector ; Fletcher, Mary A. ; Babic, Dunja Z. ; De Armas, Lesley R. ; Gupta, Sachin ; Termini, James M. ; Arheart, Kristopher L. ; Stevenson, Mario ; Tung, Frank Y. ; Fischl, Margaret A. ; Pahwa, Savita ; Stone, Geoffrey W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-84d449290043998bb6e62891bd5acc301b6df4ddbb90c638d996a6d75f04e3b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antiretroviral agents</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral Therapy, Highly Active</topic><topic>Biomarkers</topic><topic>CD38 antigen</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes</topic><topic>CD8 antigen</topic><topic>CD8-Positive 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Mario</au><au>Tung, Frank Y.</au><au>Fischl, Margaret A.</au><au>Pahwa, Savita</au><au>Stone, Geoffrey W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A therapeutic HIV-1 vaccine reduces markers of systemic immune activation and latent infection in patients under highly active antiretroviral therapy</atitle><jtitle>Vaccine</jtitle><stitle>VACCINE</stitle><addtitle>Vaccine</addtitle><date>2020-06-02</date><risdate>2020</risdate><volume>38</volume><issue>27</issue><spage>4336</spage><epage>4345</epage><pages>4336-4345</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>•Immune assays were performed on HIV-1 patients receiving therapeutic vaccine HIVAX.•HIVAX reduced the latent viral pool as measured by 2-LTR circles and total HIV-1 DNA.•HIVAX reduced serum cytokines and cellular markers of systemic immune activation.•HIVAX increased markers of activation on gag-specific CD4 + T cells.•HIVAX may suppress immune activation and latent infection in HIV-1 infected patients.
HIV infection is characterized by chronic immune activation and the establishment of a pool of latently infected cells. Antiretroviral therapy (ART) can suppress viral load to undetectable levels in peripheral blood by standard measure, however immune activation/chronic inflammation and latent infection persist and affect quality of life. We have now shown that a novel therapeutic HIV vaccine consisting of replication-defective HIV (HIVAX), given in the context of viral suppression under ART, can reduce both immune activation/chronic inflammation and latent infection. Immune activation, as measured by percent of CD8 + HLA-DR + CD38 + T cells, approached levels of healthy controls at week 16 following vaccination. Reduced immune activation was accompanied by a reduction in pro-inflammatory cytokines and peripheral α4β7 + plasmacytoid DC (a marker of mucosal immune activation). Levels of both HIV-1 DNA and 2-LTR circles were reduced at week 16 following vaccination, suggesting HIVAX can impact HIV-1 latency and reduce viral replication. Surprisingly, reduced immune activation/chronic inflammation was accompanied by an increase in the percent of memory CD4 + T cells expressing markers PD-1 and TIM-3. In addition, evaluation of HIV-1 Gag-specific CD4 + T cells for expression of 96 T cell related genes pre- and post-therapy revealed increased expression of a number of genes involved in the regulation of immune activation, T cell activation, and antiviral responses. Overall this study provides evidence that vaccination with HIVAX in subjects under long term antiviral suppression can reduce immune activation/chronic inflammation and latent infection (Clinicaltrials.gov, identifier NCT01428596).</abstract><cop>OXFORD</cop><pub>Elsevier Ltd</pub><pmid>32387010</pmid><doi>10.1016/j.vaccine.2020.04.015</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3212-1566</orcidid><orcidid>https://orcid.org/0000-0002-4470-4216</orcidid></addata></record> |
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| language | eng |
| recordid | cdi_proquest_journals_2425692088 |
| source | MEDLINE; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Access via ScienceDirect (Elsevier); ProQuest Central UK/Ireland |
| subjects | Antiretroviral agents Antiretroviral drugs Antiretroviral Therapy, Highly Active Biomarkers CD38 antigen CD4 antigen CD4-Positive T-Lymphocytes CD8 antigen CD8-Positive T-Lymphocytes Cell activation Chronic infection Cytokines Deoxyribonucleic acid DNA Drug therapy Flow cytometry Gag protein Gene expression Gene regulation Genes Highly active antiretroviral therapy Histocompatibility antigen HLA HIV HIV Infections - drug therapy HIV-1 Human immunodeficiency virus Humans Immune activation Immune responses Immunization Immunological memory Immunology Infections Inflammation Latency Latent Infection Latent viral infection Life Sciences & Biomedicine Lymphocyte Activation Lymphocytes Lymphocytes T Medicine, Research & Experimental Memory cells Mucosal immunity PD-1 protein Peripheral blood Plasma Proteins Quality of Life Replication Research & Experimental Medicine Science & Technology T-cell activation Therapeutic vaccine Therapy Vaccination Vaccines Viral Load |
| title | A therapeutic HIV-1 vaccine reduces markers of systemic immune activation and latent infection in patients under highly active antiretroviral therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-02T01%3A57%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_elsev&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20therapeutic%20HIV-1%20vaccine%20reduces%20markers%20of%20systemic%20immune%20activation%20and%20latent%20infection%20in%20patients%20under%20highly%20active%20antiretroviral%20therapy&rft.jtitle=Vaccine&rft.au=Pallikkuth,%20Suresh&rft.date=2020-06-02&rft.volume=38&rft.issue=27&rft.spage=4336&rft.epage=4345&rft.pages=4336-4345&rft.issn=0264-410X&rft.eissn=1873-2518&rft_id=info:doi/10.1016/j.vaccine.2020.04.015&rft_dat=%3Cproquest_elsev%3E2425692088%3C/proquest_elsev%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2425692088&rft_id=info:pmid/32387010&rft_els_id=S0264410X20304850&rfr_iscdi=true |