Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection
A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant...
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| creator | Lakhashe, Samir K Wang, Wendy Siddappa, Nagadenahalli B Hemashettar, Girish Polacino, Patricia Hu, Shiu-Lok Villinger, François Else, James G Novembre, Francis J Yoon, John K Lee, Sandra J Montefiori, David C Ruprecht, Ruth M Rasmussen, Robert A |
| description | A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p |
| doi_str_mv | 10.1371/journal.pone.0022010 |
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Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0022010</identifier><identifier>PMID: 21799765</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; AIDS vaccines ; Animals ; Antibodies ; Antigens ; Antiviral agents ; Biology ; Cell-mediated immunity ; Coding ; Correlation ; Divergence ; Epidemics ; Fusion Proteins, gag-pol - immunology ; Gag protein ; Glycoprotein gp160 ; Health aspects ; HIV ; HIV Envelope Protein gp160 - immunology ; HIV Infections - immunology ; HIV Infections - prevention & control ; HIV-1 - immunology ; Human immunodeficiency virus ; Humans ; Immune response (humoral) ; Immunity ; Infant ; Macaca mulatta ; Medicine ; Mucosa ; Pandemics ; Simian Immunodeficiency Virus - immunology ; tat Gene Products, Human Immunodeficiency Virus - immunology ; Tat protein ; Vaccination ; Vaccination - methods ; Vaccines ; Vaccines, Synthetic - immunology ; Viral Vaccines - immunology ; Viremia ; Viremia - prevention & control ; Viruses</subject><ispartof>PloS one, 2011-07, Vol.6 (7), p.e22010-e22010</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Lakhashe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Lakhashe et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-78cd7f98bc52cfa5072d8b74faeb0ca90192d9106318852eed0274908d04d2823</citedby><cites>FETCH-LOGICAL-c691t-78cd7f98bc52cfa5072d8b74faeb0ca90192d9106318852eed0274908d04d2823</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/PMC3140488/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140488/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21799765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Wu, Yuntao</contributor><creatorcontrib>Lakhashe, Samir K</creatorcontrib><creatorcontrib>Wang, Wendy</creatorcontrib><creatorcontrib>Siddappa, Nagadenahalli B</creatorcontrib><creatorcontrib>Hemashettar, Girish</creatorcontrib><creatorcontrib>Polacino, Patricia</creatorcontrib><creatorcontrib>Hu, Shiu-Lok</creatorcontrib><creatorcontrib>Villinger, François</creatorcontrib><creatorcontrib>Else, James G</creatorcontrib><creatorcontrib>Novembre, Francis J</creatorcontrib><creatorcontrib>Yoon, John K</creatorcontrib><creatorcontrib>Lee, Sandra J</creatorcontrib><creatorcontrib>Montefiori, David C</creatorcontrib><creatorcontrib>Ruprecht, Ruth M</creatorcontrib><creatorcontrib>Rasmussen, Robert A</creatorcontrib><title>Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>AIDS vaccines</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Antiviral agents</subject><subject>Biology</subject><subject>Cell-mediated immunity</subject><subject>Coding</subject><subject>Correlation</subject><subject>Divergence</subject><subject>Epidemics</subject><subject>Fusion Proteins, gag-pol - immunology</subject><subject>Gag protein</subject><subject>Glycoprotein gp160</subject><subject>Health aspects</subject><subject>HIV</subject><subject>HIV Envelope Protein gp160 - immunology</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - prevention & control</subject><subject>HIV-1 - immunology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immune response (humoral)</subject><subject>Immunity</subject><subject>Infant</subject><subject>Macaca mulatta</subject><subject>Medicine</subject><subject>Mucosa</subject><subject>Pandemics</subject><subject>Simian Immunodeficiency Virus - immunology</subject><subject>tat Gene Products, Human Immunodeficiency Virus - immunology</subject><subject>Tat protein</subject><subject>Vaccination</subject><subject>Vaccination - methods</subject><subject>Vaccines</subject><subject>Vaccines, Synthetic - immunology</subject><subject>Viral Vaccines - immunology</subject><subject>Viremia</subject><subject>Viremia - prevention & control</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1GL1DAUhYso7jr6D0QLguLDjEmaNokPwjKoO7CwsKvzGtLkttMh09SkXfTfm5npLlPZB-lDS-53TtJzb5LkNUYLnDH8aesG3yq76FwLC4QIQRg9Sc6xyMi8ICh7evJ9lrwIYYtQnvGieJ6cEcyEYEV-nlRrpXXTqr5xbapq1bShTzfQg3fW1W4I6U2eaqsMpMv09nK1_px2Hu6gPQhclTZtBfqobk2qnfdgVQ9hX-u864_Fl8mzStkAr8b3LPn57euP5eX86vr7anlxNdeFwP2ccW1YJXipc6IrlSNGDC8ZrRSUSCuBsCBGYFRkmPOcABhEGBWIG0QN4SSbJW-Pvp11QY4RBYkzVBDKY0SRWB0J49RWdr7ZKf9HOtXIw4LztVS-b7QFyVmOjREFY3lOKfCyyAwqcJVpoVlpVPT6Mu42lDswOqbilZ2YTitts5G1u5MZpohyHg0-jAbe_Rog9HLXBA3WqhZi9pLzeGKRx77Nknf_kI__3EjVKp4_tsbFbfXeU15QVnBO6YFaPELFx8Cu0XGcqiauTwQfJ4LI9PC7r9UQglzd3vw_e72esu9P2A0o22-Cs8N-YsIUpEdQexeCh-ohY4zk_jbcpyH3t0GOtyHK3pz250F0P_7ZX7HXA_Y</recordid><startdate>20110720</startdate><enddate>20110720</enddate><creator>Lakhashe, Samir K</creator><creator>Wang, Wendy</creator><creator>Siddappa, Nagadenahalli B</creator><creator>Hemashettar, Girish</creator><creator>Polacino, Patricia</creator><creator>Hu, Shiu-Lok</creator><creator>Villinger, François</creator><creator>Else, James G</creator><creator>Novembre, Francis J</creator><creator>Yoon, John K</creator><creator>Lee, Sandra J</creator><creator>Montefiori, David C</creator><creator>Ruprecht, Ruth M</creator><creator>Rasmussen, Robert A</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110720</creationdate><title>Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection</title><author>Lakhashe, Samir K ; Wang, Wendy ; Siddappa, Nagadenahalli B ; Hemashettar, Girish ; Polacino, Patricia ; Hu, Shiu-Lok ; Villinger, François ; Else, James G ; Novembre, Francis J ; Yoon, John K ; Lee, Sandra J ; Montefiori, David C ; Ruprecht, Ruth M ; Rasmussen, Robert A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-78cd7f98bc52cfa5072d8b74faeb0ca90192d9106318852eed0274908d04d2823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>AIDS</topic><topic>AIDS vaccines</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Antiviral agents</topic><topic>Biology</topic><topic>Cell-mediated immunity</topic><topic>Coding</topic><topic>Correlation</topic><topic>Divergence</topic><topic>Epidemics</topic><topic>Fusion Proteins, gag-pol - immunology</topic><topic>Gag protein</topic><topic>Glycoprotein gp160</topic><topic>Health aspects</topic><topic>HIV</topic><topic>HIV Envelope Protein gp160 - immunology</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - prevention & control</topic><topic>HIV-1 - immunology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immune response (humoral)</topic><topic>Immunity</topic><topic>Infant</topic><topic>Macaca mulatta</topic><topic>Medicine</topic><topic>Mucosa</topic><topic>Pandemics</topic><topic>Simian Immunodeficiency Virus - immunology</topic><topic>tat Gene Products, Human Immunodeficiency Virus - immunology</topic><topic>Tat protein</topic><topic>Vaccination</topic><topic>Vaccination - methods</topic><topic>Vaccines</topic><topic>Vaccines, Synthetic - immunology</topic><topic>Viral Vaccines - immunology</topic><topic>Viremia</topic><topic>Viremia - prevention & control</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lakhashe, Samir K</creatorcontrib><creatorcontrib>Wang, Wendy</creatorcontrib><creatorcontrib>Siddappa, Nagadenahalli B</creatorcontrib><creatorcontrib>Hemashettar, Girish</creatorcontrib><creatorcontrib>Polacino, Patricia</creatorcontrib><creatorcontrib>Hu, Shiu-Lok</creatorcontrib><creatorcontrib>Villinger, François</creatorcontrib><creatorcontrib>Else, James G</creatorcontrib><creatorcontrib>Novembre, Francis J</creatorcontrib><creatorcontrib>Yoon, John K</creatorcontrib><creatorcontrib>Lee, Sandra J</creatorcontrib><creatorcontrib>Montefiori, David C</creatorcontrib><creatorcontrib>Ruprecht, Ruth M</creatorcontrib><creatorcontrib>Rasmussen, Robert A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21799765</pmid><doi>10.1371/journal.pone.0022010</doi><tpages>e22010</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-07, Vol.6 (7), p.e22010-e22010 |
| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acquired immune deficiency syndrome AIDS AIDS vaccines Animals Antibodies Antigens Antiviral agents Biology Cell-mediated immunity Coding Correlation Divergence Epidemics Fusion Proteins, gag-pol - immunology Gag protein Glycoprotein gp160 Health aspects HIV HIV Envelope Protein gp160 - immunology HIV Infections - immunology HIV Infections - prevention & control HIV-1 - immunology Human immunodeficiency virus Humans Immune response (humoral) Immunity Infant Macaca mulatta Medicine Mucosa Pandemics Simian Immunodeficiency Virus - immunology tat Gene Products, Human Immunodeficiency Virus - immunology Tat protein Vaccination Vaccination - methods Vaccines Vaccines, Synthetic - immunology Viral Vaccines - immunology Viremia Viremia - prevention & control Viruses |
| title | Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T05%3A43%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Vaccination%20against%20heterologous%20R5%20clade%20C%20SHIV:%20prevention%20of%20infection%20and%20correlates%20of%20protection&rft.jtitle=PloS%20one&rft.au=Lakhashe,%20Samir%20K&rft.date=2011-07-20&rft.volume=6&rft.issue=7&rft.spage=e22010&rft.epage=e22010&rft.pages=e22010-e22010&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0022010&rft_dat=%3Cgale_plos_%3EA476884401%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1306248201&rft_id=info:pmid/21799765&rft_galeid=A476884401&rft_doaj_id=oai_doaj_org_article_8751dd96775544e8b63d061f3c9c7bda&rfr_iscdi=true |