HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site
Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to...
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| creator | McCurley, Nathanael P Domi, Arban Basu, Rahul Saunders, Kevin O LaBranche, Celia C Montefiori, David C Haynes, Barton F Robinson, Harriet L |
| description | Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs. |
| doi_str_mv | 10.1371/journal.pone.0177863 |
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The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0177863</identifier><identifier>PMID: 29020058</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; AIDS Vaccines - immunology ; Amino acids ; Animals ; Antibodies ; Antibodies, Neutralizing - immunology ; Antibody Formation - immunology ; Antigenicity ; Antigens ; Binding Sites ; Biology and Life Sciences ; Care and treatment ; CD4 antigen ; CD4 Antigens - metabolism ; Deoxyribonucleic acid ; Diagnosis ; DNA ; DNA vaccines ; Dosage and administration ; Drug delivery systems ; env Gene Products, Human Immunodeficiency Virus - metabolism ; Epitopes ; F protein ; Female ; Fibroblasts ; Glycoprotein gp120 ; HEK293 Cells ; HIV ; HIV Antigens - immunology ; HIV Infections - immunology ; HIV Infections - transmission ; Human immunodeficiency virus ; Humans ; Immunogenicity ; Immunoglobulins ; Infections ; Inoculation ; Macaca mulatta ; Medicine and Health Sciences ; Mutation ; Neutralization ; Neutralizing ; Research and analysis methods ; Vaccination ; Vaccines ; Vaccines, DNA - immunology ; Vaccinia ; Vaccinia virus - immunology ; Vaccinia virus - ultrastructure ; Virus-like particles ; Viruses</subject><ispartof>PloS one, 2017-10, Vol.12 (10), p.e0177863-e0177863</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 McCurley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (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>2017 McCurley et al 2017 McCurley et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-aa238bfe165b3c4b901b6545d86c9e54b7102d86136327fd02bd23fa85e27fdd3</citedby><cites>FETCH-LOGICAL-c692t-aa238bfe165b3c4b901b6545d86c9e54b7102d86136327fd02bd23fa85e27fdd3</cites><orcidid>0000-0001-6380-3458</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636061/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636061/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29020058$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCurley, Nathanael P</creatorcontrib><creatorcontrib>Domi, Arban</creatorcontrib><creatorcontrib>Basu, Rahul</creatorcontrib><creatorcontrib>Saunders, Kevin O</creatorcontrib><creatorcontrib>LaBranche, Celia C</creatorcontrib><creatorcontrib>Montefiori, David C</creatorcontrib><creatorcontrib>Haynes, Barton F</creatorcontrib><creatorcontrib>Robinson, Harriet L</creatorcontrib><title>HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. 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Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>AIDS Vaccines - immunology</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibody Formation - immunology</subject><subject>Antigenicity</subject><subject>Antigens</subject><subject>Binding Sites</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>CD4 antigen</subject><subject>CD4 Antigens - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnosis</subject><subject>DNA</subject><subject>DNA vaccines</subject><subject>Dosage and administration</subject><subject>Drug delivery systems</subject><subject>env Gene Products, Human Immunodeficiency Virus - metabolism</subject><subject>Epitopes</subject><subject>F protein</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Glycoprotein gp120</subject><subject>HEK293 Cells</subject><subject>HIV</subject><subject>HIV Antigens - immunology</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - transmission</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunogenicity</subject><subject>Immunoglobulins</subject><subject>Infections</subject><subject>Inoculation</subject><subject>Macaca mulatta</subject><subject>Medicine and Health Sciences</subject><subject>Mutation</subject><subject>Neutralization</subject><subject>Neutralizing</subject><subject>Research and analysis methods</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccinia</subject><subject>Vaccinia virus - immunology</subject><subject>Vaccinia virus - ultrastructure</subject><subject>Virus-like particles</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0tr3DAQx01padJtv0FpDYXSHnajt-1LIWwfWQgE-shVyNJ4V4tX2lpyaPvpK2edsC45FB_k0fz-o5mRJsteYrTAtMBnW993TrWLvXewQLgoSkEfZae4omQuCKKPj_5PsmchbBHitBTiaXZCKkSSVZ5m24vVdR475cLOxgjmrPG9M9DlN0pr6yDk0FptY6766Fu_9n3Io01-kjvok7C1f6xb58pFW3tjk6DxXR43kC8_sry2zgzuYCM8z540qg3wYlxn2Y_Pn74vL-aXV19Wy_PLuRYViXOlCC3rBrDgNdWsrhCuBWfclEJXwFldYESSgamgpGgMIrUhtFElh8E0dJa9PsTdtz7IsU1B4oojxJhgRSJWB8J4tZX7zu5U91t6ZeXthu_WUnXR6hakaBQUBCNACjPdcMWUKbCoBE9pVAVPsT6Mp_X1DowGNzRlEnTqcXYj1_5GckEFSlXMsndjgM7_7CFEubNBQ9sqB6nbt3kzXOJyyPvNP-jD1Y3UWqUCrGt8OlcPQeU5RxWmSDCaqMUDVPoM7KxOb6qxaX8ieD8RJCbCr7hWfQhy9e3r_7NX11P27RG7AdXGTfBtH613YQqyA6g7H0IHzX2TMZLDSNx1Qw4jIceRSLJXxxd0L7qbAfoXfMoF5Q</recordid><startdate>20171011</startdate><enddate>20171011</enddate><creator>McCurley, Nathanael P</creator><creator>Domi, Arban</creator><creator>Basu, Rahul</creator><creator>Saunders, Kevin O</creator><creator>LaBranche, Celia C</creator><creator>Montefiori, David C</creator><creator>Haynes, Barton F</creator><creator>Robinson, Harriet L</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>AEUYN</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><orcidid>https://orcid.org/0000-0001-6380-3458</orcidid></search><sort><creationdate>20171011</creationdate><title>HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site</title><author>McCurley, Nathanael P ; Domi, Arban ; Basu, Rahul ; Saunders, Kevin O ; LaBranche, Celia C ; Montefiori, David C ; Haynes, Barton F ; Robinson, Harriet L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-aa238bfe165b3c4b901b6545d86c9e54b7102d86136327fd02bd23fa85e27fdd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>AIDS</topic><topic>AIDS Vaccines - 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The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29020058</pmid><doi>10.1371/journal.pone.0177863</doi><tpages>e0177863</tpages><orcidid>https://orcid.org/0000-0001-6380-3458</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2017-10, Vol.12 (10), p.e0177863-e0177863 |
| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) Journals Open Acc |
| subjects | Acquired immune deficiency syndrome AIDS AIDS Vaccines - immunology Amino acids Animals Antibodies Antibodies, Neutralizing - immunology Antibody Formation - immunology Antigenicity Antigens Binding Sites Biology and Life Sciences Care and treatment CD4 antigen CD4 Antigens - metabolism Deoxyribonucleic acid Diagnosis DNA DNA vaccines Dosage and administration Drug delivery systems env Gene Products, Human Immunodeficiency Virus - metabolism Epitopes F protein Female Fibroblasts Glycoprotein gp120 HEK293 Cells HIV HIV Antigens - immunology HIV Infections - immunology HIV Infections - transmission Human immunodeficiency virus Humans Immunogenicity Immunoglobulins Infections Inoculation Macaca mulatta Medicine and Health Sciences Mutation Neutralization Neutralizing Research and analysis methods Vaccination Vaccines Vaccines, DNA - immunology Vaccinia Vaccinia virus - immunology Vaccinia virus - ultrastructure Virus-like particles Viruses |
| title | HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T13%3A02%3A36IST&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=HIV%20transmitted/founder%20vaccines%20elicit%20autologous%20tier%202%20neutralizing%20antibodies%20for%20the%20CD4%20binding%20site&rft.jtitle=PloS%20one&rft.au=McCurley,%20Nathanael%20P&rft.date=2017-10-11&rft.volume=12&rft.issue=10&rft.spage=e0177863&rft.epage=e0177863&rft.pages=e0177863-e0177863&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0177863&rft_dat=%3Cgale_plos_%3EA509130643%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=1950044647&rft_id=info:pmid/29020058&rft_galeid=A509130643&rft_doaj_id=oai_doaj_org_article_6fae7210e0a14cf5a4ad716965710975&rfr_iscdi=true |