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Sci Rep. 2015 Sep 10;5:13926. doi: 10.1038/srep13926.

Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining.

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Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX, USA.
Department of Biodefense and Protein Diagnostics, Luminex Corporation, Austin, TX, USA.
Center for Systems and Synthetic Biology University of Texas at Austin, Austin, TX, USA.
Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX, USA.
Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA.


The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different Ebolaviruses. We developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the VH:VL paired antibody repertoire encoded by highly expanded B cells in the draining popliteal lymph node (PLN). This approach requires neither screening nor selection for antigen-binding. Specifically we show that mouse immunization with Ebola VLPs gives rise to a highly polarized antibody repertoire in CD138(+) antibody-secreting cells within the PLN. All highly expanded antibody clones (7/7 distinct clones/animal) were expressed recombinantly, and shown to recognize the VLPs used for immunization. Using this approach we obtained diverse panels of antibodies including: (i) antibodies with high affinity towards GP; (ii) antibodies which bound Ebola VLP Kissidougou-C15, the strain circulating in the recent West African outbreak; (iii) non-GP binding antibodies that recognize wild type Sudan or Bundibugyo viruses that have 39% and 37% sequence divergence from Ebola virus, respectively and (iv) antibodies to the Reston virus GP for which no antibodies have been reported.

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