Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1: e1004552
To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llama...
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| Veröffentlicht in: | PLoS pathogens 2014-12, Vol.10 (12) |
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| creator | McCoy, Laura E Rutten, Lucy Frampton, Dan Anderson, Ian Granger, Luke Bashford-Rogers, Rachael Dekkers, Gillian Strokappe, Nika M Seaman, Michael S Koh, Willie Grippo, Vanina Kliche, Alexander Verrips, Theo Kellam, Paul Fassati, Ariberto Weiss, Robin A |
| description | To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols. |
| doi_str_mv | 10.1371/journal.ppat.1004552 |
| format | Article |
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In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.</description><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1004552</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; Animals ; Immunization ; Infections ; Methods ; Neutralization ; Vaccines</subject><ispartof>PLoS pathogens, 2014-12, Vol.10 (12)</ispartof><rights>2014 Public Library of Science. 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Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>Animals</subject><subject>Immunization</subject><subject>Infections</subject><subject>Methods</subject><subject>Neutralization</subject><subject>Vaccines</subject><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNqNjs1qAjEURoO0UKu-QRcXup7pXGeSqctqFQvaTaU7kehEG4m50_wI-vQqiGtX37c4HA5jL5ilmJf4tqXorDRpXcuQYpYVnHcbrImc50mZl8XD7QvxxJ69354ZzFE02XxKRq2ikQ6GezIxaLJAa-g7kpU5wLeKwUmjj9puYGLkTsKHDXpJlVYeAkH4UzD4LJK-ttWF-dFBXQTjr98E2-xxLY1Xneu22OtoOBuMk9rRf1Q-LK7pfoHinXd7mTh33kedABZzS38</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>McCoy, Laura E</creator><creator>Rutten, Lucy</creator><creator>Frampton, Dan</creator><creator>Anderson, Ian</creator><creator>Granger, Luke</creator><creator>Bashford-Rogers, Rachael</creator><creator>Dekkers, Gillian</creator><creator>Strokappe, Nika M</creator><creator>Seaman, Michael S</creator><creator>Koh, Willie</creator><creator>Grippo, Vanina</creator><creator>Kliche, Alexander</creator><creator>Verrips, Theo</creator><creator>Kellam, Paul</creator><creator>Fassati, Ariberto</creator><creator>Weiss, Robin A</creator><general>Public Library of Science</general><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20141201</creationdate><title>Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1</title><author>McCoy, Laura E ; 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however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. 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| subjects | Acquired immune deficiency syndrome AIDS Animals Immunization Infections Methods Neutralization Vaccines |
| title | Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1: e1004552 |
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