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

Bo Wang, Christien A. Kluwe, Oana I. Lungu, Brandon J. DeKosky, Scott A. Kerr, Erik L. Johnson, Jiwon Jung, Alec B. Rezigh, Sean M. Carroll, Ann N. Reyes, Janelle R. Bentz, Itamar Villanueva, Amy L. Altman, Robert A. Davey, Andrew D. Ellington, George Georgiou

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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 V H:V L 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.

Original languageEnglish (US)
Article number13926
JournalScientific reports
Volume5
DOIs
StatePublished - Sep 10 2015
Externally publishedYes

ASJC Scopus subject areas

  • General

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