Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1.
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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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1004552 |
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| author | Laura E McCoy Lucy Rutten Dan Frampton Ian Anderson Luke Granger Rachael Bashford-Rogers Gillian Dekkers Nika M Strokappe Michael S Seaman Willie Koh Vanina Grippo Alexander Kliche Theo Verrips Paul Kellam Ariberto Fassati Robin A Weiss |
| author_facet | Laura E McCoy Lucy Rutten Dan Frampton Ian Anderson Luke Granger Rachael Bashford-Rogers Gillian Dekkers Nika M Strokappe Michael S Seaman Willie Koh Vanina Grippo Alexander Kliche Theo Verrips Paul Kellam Ariberto Fassati Robin A Weiss |
| author_sort | Laura E McCoy |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-83f2d3d6e15349dfb005fad45ed70627 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2014-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-83f2d3d6e15349dfb005fad45ed706272025-08-20T02:34:10ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-12-011012e100455210.1371/journal.ppat.1004552Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1.Laura E McCoyLucy RuttenDan FramptonIan AndersonLuke GrangerRachael Bashford-RogersGillian DekkersNika M StrokappeMichael S SeamanWillie KohVanina GrippoAlexander KlicheTheo VerripsPaul KellamAriberto FassatiRobin A WeissTo 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.https://doi.org/10.1371/journal.ppat.1004552 |
| spellingShingle | Laura E McCoy Lucy Rutten Dan Frampton Ian Anderson Luke Granger Rachael Bashford-Rogers Gillian Dekkers Nika M Strokappe Michael S Seaman Willie Koh Vanina Grippo Alexander Kliche Theo Verrips Paul Kellam Ariberto Fassati Robin A Weiss Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1. PLoS Pathogens |
| title | Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1. |
| title_full | Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1. |
| title_fullStr | Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1. |
| title_full_unstemmed | Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1. |
| title_short | Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1. |
| title_sort | molecular evolution of broadly neutralizing llama antibodies to the cd4 binding site of hiv 1 |
| url | https://doi.org/10.1371/journal.ppat.1004552 |
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