Rapid development of glycan-specific, broad, and potent anti–HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque
It is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be a critical component of a successful vaccine against HIV. A significant fraction of HIV-infected individuals mount bNAb responses, providing support for the notion that such responses could be elicite...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2011-12, Vol.108 (50), p.20125-20129 |
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| creator | Walker, Laura M Sok, Devin Nishimura, Yoshiaki Donau, Olivia Sadjadpour, Reza Gautam, Rajeev Shingai, Masashi Pejchal, Robert Ramos, Alejandra Simek, Melissa D Geng, Yu Wilson, Ian A Poignard, Pascal Martin, Malcolm A Burton, Dennis R |
| description | It is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be a critical component of a successful vaccine against HIV. A significant fraction of HIV-infected individuals mount bNAb responses, providing support for the notion that such responses could be elicited through vaccination. Infection of macaques with simian immunodeficiency virus (SIV) or SIV/HIV chimeric virus (SHIV) has been widely used to model aspects of HIV infection, but to date, only limited bNAb responses have been described. Here, we screened plasma from 14 R5-tropic SHIV-infected macaques for broadly neutralizing activity and identified a macaque with highly potent cross-clade plasma NAb response. Longitudinal studies showed that the development of broad and autologous NAb responses occurred coincidentally in this animal. Serum-mapping studies, using pseudovirus point mutants and antigen adsorption assays, indicated that the plasma bNAbs are specific for epitopes that include carbohydrates and are critically dependent on the glycan at position 332 of Env gp120. The results described herein provide insight into the development and evolution of a broad response, suggest that certain bNAb specificities may be more rapidly induced by immunization than others, and provide a potential model for the facile study of the development of bNAb responses. |
| doi_str_mv | 10.1073/pnas.1117531108 |
| format | Article |
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A significant fraction of HIV-infected individuals mount bNAb responses, providing support for the notion that such responses could be elicited through vaccination. Infection of macaques with simian immunodeficiency virus (SIV) or SIV/HIV chimeric virus (SHIV) has been widely used to model aspects of HIV infection, but to date, only limited bNAb responses have been described. Here, we screened plasma from 14 R5-tropic SHIV-infected macaques for broadly neutralizing activity and identified a macaque with highly potent cross-clade plasma NAb response. Longitudinal studies showed that the development of broad and autologous NAb responses occurred coincidentally in this animal. Serum-mapping studies, using pseudovirus point mutants and antigen adsorption assays, indicated that the plasma bNAbs are specific for epitopes that include carbohydrates and are critically dependent on the glycan at position 332 of Env gp120. The results described herein provide insight into the development and evolution of a broad response, suggest that certain bNAb specificities may be more rapidly induced by immunization than others, and provide a potential model for the facile study of the development of bNAb responses.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1117531108</identifier><identifier>PMID: 22123961</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adsorption ; Animals ; Antibodies ; Antibodies, Neutralizing - blood ; Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Antibody Specificity - immunology ; Antiviral agents ; Biological Sciences ; Carbohydrates ; Epitopes ; Evolution ; Glycoprotein gp120 ; HIV ; HIV - immunology ; HIV 1 ; HIV Envelope Protein gp120 - immunology ; HIV Infections - blood ; HIV Infections - immunology ; HIV Infections - virology ; Human immunodeficiency virus ; Immunization ; Immunoglobulins ; Infection ; Infections ; Inhibitory concentration 50 ; longitudinal studies ; Macaca ; Macaca - blood ; Macaca - immunology ; Macaca - virology ; Monkeys & apes ; mutants ; Mutation ; neutralization ; Neutralization Tests ; Neutralizing antibodies ; Polysaccharides ; Polysaccharides - immunology ; Protein Binding ; Recombination, Genetic - genetics ; Shivs ; Simian Acquired Immunodeficiency Syndrome - blood ; Simian Acquired Immunodeficiency Syndrome - immunology ; Simian Acquired Immunodeficiency Syndrome - virology ; Simian immunodeficiency virus ; Simian Immunodeficiency Virus - immunology ; Vaccination ; Vaccines ; Viruses</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2011-12, Vol.108 (50), p.20125-20129</ispartof><rights>copyright © 1993—2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Dec 13, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-4778a1ebd0e35d3d6bf05500a8ee8e2307ff0cfb1611d0dd3bfcf694933d2413</citedby><cites>FETCH-LOGICAL-c522t-4778a1ebd0e35d3d6bf05500a8ee8e2307ff0cfb1611d0dd3bfcf694933d2413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/108/50.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23060086$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23060086$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27929,27930,53796,53798,58022,58255</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22123961$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walker, Laura M</creatorcontrib><creatorcontrib>Sok, Devin</creatorcontrib><creatorcontrib>Nishimura, Yoshiaki</creatorcontrib><creatorcontrib>Donau, Olivia</creatorcontrib><creatorcontrib>Sadjadpour, Reza</creatorcontrib><creatorcontrib>Gautam, Rajeev</creatorcontrib><creatorcontrib>Shingai, Masashi</creatorcontrib><creatorcontrib>Pejchal, Robert</creatorcontrib><creatorcontrib>Ramos, Alejandra</creatorcontrib><creatorcontrib>Simek, Melissa D</creatorcontrib><creatorcontrib>Geng, Yu</creatorcontrib><creatorcontrib>Wilson, Ian A</creatorcontrib><creatorcontrib>Poignard, Pascal</creatorcontrib><creatorcontrib>Martin, Malcolm A</creatorcontrib><creatorcontrib>Burton, Dennis R</creatorcontrib><title>Rapid development of glycan-specific, broad, and potent anti–HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>It is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be a critical component of a successful vaccine against HIV. A significant fraction of HIV-infected individuals mount bNAb responses, providing support for the notion that such responses could be elicited through vaccination. Infection of macaques with simian immunodeficiency virus (SIV) or SIV/HIV chimeric virus (SHIV) has been widely used to model aspects of HIV infection, but to date, only limited bNAb responses have been described. Here, we screened plasma from 14 R5-tropic SHIV-infected macaques for broadly neutralizing activity and identified a macaque with highly potent cross-clade plasma NAb response. Longitudinal studies showed that the development of broad and autologous NAb responses occurred coincidentally in this animal. Serum-mapping studies, using pseudovirus point mutants and antigen adsorption assays, indicated that the plasma bNAbs are specific for epitopes that include carbohydrates and are critically dependent on the glycan at position 332 of Env gp120. The results described herein provide insight into the development and evolution of a broad response, suggest that certain bNAb specificities may be more rapidly induced by immunization than others, and provide a potential model for the facile study of the development of bNAb responses.</description><subject>Adsorption</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>Antibody Specificity - immunology</subject><subject>Antiviral agents</subject><subject>Biological Sciences</subject><subject>Carbohydrates</subject><subject>Epitopes</subject><subject>Evolution</subject><subject>Glycoprotein gp120</subject><subject>HIV</subject><subject>HIV - immunology</subject><subject>HIV 1</subject><subject>HIV Envelope Protein gp120 - immunology</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>Human immunodeficiency virus</subject><subject>Immunization</subject><subject>Immunoglobulins</subject><subject>Infection</subject><subject>Infections</subject><subject>Inhibitory concentration 50</subject><subject>longitudinal studies</subject><subject>Macaca</subject><subject>Macaca - blood</subject><subject>Macaca - immunology</subject><subject>Macaca - virology</subject><subject>Monkeys & apes</subject><subject>mutants</subject><subject>Mutation</subject><subject>neutralization</subject><subject>Neutralization Tests</subject><subject>Neutralizing antibodies</subject><subject>Polysaccharides</subject><subject>Polysaccharides - immunology</subject><subject>Protein Binding</subject><subject>Recombination, Genetic - genetics</subject><subject>Shivs</subject><subject>Simian Acquired Immunodeficiency Syndrome - blood</subject><subject>Simian Acquired Immunodeficiency Syndrome - immunology</subject><subject>Simian Acquired Immunodeficiency Syndrome - virology</subject><subject>Simian immunodeficiency virus</subject><subject>Simian Immunodeficiency Virus - immunology</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Viruses</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhSMEoqWwZgVYbNg0nXvt_G6QUAV0pEpIbenWcvwz9SiJUzsZqax4h74hT4LDDB1gw8qyzneOjq2TJC8RThBKthh6EU4QscwZIlSPkkOEGtMiq-FxcghAy7TKaHaQPAthDQB1XsHT5IBSpKwu8DC5vxCDVUTpjW7d0Ol-JM6QVXsnRZ-GQUtrrDwmjXdCHRPRKzK4caZEP9of3-_PltcpktWAFEivp9GL1n6z_eqX3jhldSC2jzdykZPL5fUiGoi8sZ32VpKN9dOsGy1HrUgnpLid9PPkiRFt0C9251Fy9enj1elZev7l8_L0w3kqc0rHNCvLSqBuFGiWK6aKxkCeA4hK60pTBqUxIE2DBaICpVhjpCnqrGZM0QzZUfJ-GztMTaeVjK-K7fngbSf8HXfC8r-V3t7wldtwRnPAEmLAu12Ad7F2GHlng9RtK3rtpsBrCmVV0az6P4lYZwh0LvX2H3LtJt_Hb4gQ1GWZF3WEFltIeheC1-ahNAKfd8HnXfD9LqLj9Z9vfeB_DyECZAfMzn1cxXPgFJDmEXm1RdZhdH4fwaAAqIqov9nqRjguVt4G_vUyWrO4uwopLdlPhVTSjA</recordid><startdate>20111213</startdate><enddate>20111213</enddate><creator>Walker, Laura M</creator><creator>Sok, Devin</creator><creator>Nishimura, Yoshiaki</creator><creator>Donau, Olivia</creator><creator>Sadjadpour, Reza</creator><creator>Gautam, Rajeev</creator><creator>Shingai, Masashi</creator><creator>Pejchal, Robert</creator><creator>Ramos, Alejandra</creator><creator>Simek, Melissa D</creator><creator>Geng, Yu</creator><creator>Wilson, Ian A</creator><creator>Poignard, Pascal</creator><creator>Martin, Malcolm A</creator><creator>Burton, Dennis R</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20111213</creationdate><title>Rapid development of glycan-specific, broad, and potent anti–HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque</title><author>Walker, Laura M ; Sok, Devin ; Nishimura, Yoshiaki ; Donau, Olivia ; Sadjadpour, Reza ; Gautam, Rajeev ; Shingai, Masashi ; Pejchal, Robert ; Ramos, Alejandra ; Simek, Melissa D ; Geng, Yu ; Wilson, Ian A ; Poignard, Pascal ; Martin, Malcolm A ; Burton, Dennis R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-4778a1ebd0e35d3d6bf05500a8ee8e2307ff0cfb1611d0dd3bfcf694933d2413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adsorption</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Neutralizing - blood</topic><topic>Antibodies, Neutralizing - immunology</topic><topic>Antibodies, Viral - immunology</topic><topic>Antibody Specificity - immunology</topic><topic>Antiviral agents</topic><topic>Biological Sciences</topic><topic>Carbohydrates</topic><topic>Epitopes</topic><topic>Evolution</topic><topic>Glycoprotein gp120</topic><topic>HIV</topic><topic>HIV - immunology</topic><topic>HIV 1</topic><topic>HIV Envelope Protein gp120 - immunology</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - virology</topic><topic>Human immunodeficiency virus</topic><topic>Immunization</topic><topic>Immunoglobulins</topic><topic>Infection</topic><topic>Infections</topic><topic>Inhibitory concentration 50</topic><topic>longitudinal studies</topic><topic>Macaca</topic><topic>Macaca - blood</topic><topic>Macaca - immunology</topic><topic>Macaca - virology</topic><topic>Monkeys & apes</topic><topic>mutants</topic><topic>Mutation</topic><topic>neutralization</topic><topic>Neutralization Tests</topic><topic>Neutralizing antibodies</topic><topic>Polysaccharides</topic><topic>Polysaccharides - immunology</topic><topic>Protein Binding</topic><topic>Recombination, Genetic - genetics</topic><topic>Shivs</topic><topic>Simian Acquired Immunodeficiency Syndrome - blood</topic><topic>Simian Acquired Immunodeficiency Syndrome - immunology</topic><topic>Simian Acquired Immunodeficiency Syndrome - virology</topic><topic>Simian immunodeficiency virus</topic><topic>Simian Immunodeficiency Virus - immunology</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walker, Laura M</creatorcontrib><creatorcontrib>Sok, Devin</creatorcontrib><creatorcontrib>Nishimura, Yoshiaki</creatorcontrib><creatorcontrib>Donau, Olivia</creatorcontrib><creatorcontrib>Sadjadpour, Reza</creatorcontrib><creatorcontrib>Gautam, Rajeev</creatorcontrib><creatorcontrib>Shingai, Masashi</creatorcontrib><creatorcontrib>Pejchal, Robert</creatorcontrib><creatorcontrib>Ramos, Alejandra</creatorcontrib><creatorcontrib>Simek, Melissa D</creatorcontrib><creatorcontrib>Geng, Yu</creatorcontrib><creatorcontrib>Wilson, Ian A</creatorcontrib><creatorcontrib>Poignard, Pascal</creatorcontrib><creatorcontrib>Martin, Malcolm A</creatorcontrib><creatorcontrib>Burton, Dennis R</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walker, Laura M</au><au>Sok, Devin</au><au>Nishimura, Yoshiaki</au><au>Donau, Olivia</au><au>Sadjadpour, Reza</au><au>Gautam, Rajeev</au><au>Shingai, Masashi</au><au>Pejchal, Robert</au><au>Ramos, Alejandra</au><au>Simek, Melissa D</au><au>Geng, Yu</au><au>Wilson, Ian A</au><au>Poignard, Pascal</au><au>Martin, Malcolm A</au><au>Burton, Dennis R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid development of glycan-specific, broad, and potent anti–HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2011-12-13</date><risdate>2011</risdate><volume>108</volume><issue>50</issue><spage>20125</spage><epage>20129</epage><pages>20125-20129</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>It is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be a critical component of a successful vaccine against HIV. A significant fraction of HIV-infected individuals mount bNAb responses, providing support for the notion that such responses could be elicited through vaccination. Infection of macaques with simian immunodeficiency virus (SIV) or SIV/HIV chimeric virus (SHIV) has been widely used to model aspects of HIV infection, but to date, only limited bNAb responses have been described. Here, we screened plasma from 14 R5-tropic SHIV-infected macaques for broadly neutralizing activity and identified a macaque with highly potent cross-clade plasma NAb response. Longitudinal studies showed that the development of broad and autologous NAb responses occurred coincidentally in this animal. Serum-mapping studies, using pseudovirus point mutants and antigen adsorption assays, indicated that the plasma bNAbs are specific for epitopes that include carbohydrates and are critically dependent on the glycan at position 332 of Env gp120. The results described herein provide insight into the development and evolution of a broad response, suggest that certain bNAb specificities may be more rapidly induced by immunization than others, and provide a potential model for the facile study of the development of bNAb responses.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22123961</pmid><doi>10.1073/pnas.1117531108</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adsorption Animals Antibodies Antibodies, Neutralizing - blood Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Antibody Specificity - immunology Antiviral agents Biological Sciences Carbohydrates Epitopes Evolution Glycoprotein gp120 HIV HIV - immunology HIV 1 HIV Envelope Protein gp120 - immunology HIV Infections - blood HIV Infections - immunology HIV Infections - virology Human immunodeficiency virus Immunization Immunoglobulins Infection Infections Inhibitory concentration 50 longitudinal studies Macaca Macaca - blood Macaca - immunology Macaca - virology Monkeys & apes mutants Mutation neutralization Neutralization Tests Neutralizing antibodies Polysaccharides Polysaccharides - immunology Protein Binding Recombination, Genetic - genetics Shivs Simian Acquired Immunodeficiency Syndrome - blood Simian Acquired Immunodeficiency Syndrome - immunology Simian Acquired Immunodeficiency Syndrome - virology Simian immunodeficiency virus Simian Immunodeficiency Virus - immunology Vaccination Vaccines Viruses |
| title | Rapid development of glycan-specific, broad, and potent anti–HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque |
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