McCoy, Laura E. and Rutten, Lucy and Frampton, Dan and Anderson, Ian and Granger, Luke and Bashford-Rogers, Rachael and Dekkers, Gillian and Strokappe, Nika M. and Seaman, Michael S. and Koh, Willie and Grippo, Vanina and Kliche, Alexander and Verrips, Theo and Kellam, Paul and Fassati, Ariberto and Weiss, Robin A. (2014) Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1. PLOS PATHOGENS, 10 (12): e1004552. ISSN 1553-7366, 1553-7374
Full text not available from this repository. (Request a copy)Abstract
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 mu g/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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | B-CELL RECEPTORS; MONOCLONAL-ANTIBODIES; STRUCTURAL BASIS; IN-VIVO; VECTORED IMMUNOPROPHYLAXIS; SHIV TRANSMISSION; ENVELOPE PROTEIN; RATIONAL DESIGN; HUMANIZED MICE; POTENT; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Aug 2019 11:05 |
| Last Modified: | 07 Aug 2019 11:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9115 |
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