Generation and characterization of protective antibodies to Marburg virus

Jeffrey W. Froude, Thibaut Pelat, Sebastian Miethe, Samantha E. Zak, Anna Z. Wec, Kartik Chandran, Jennifer Mary Brannan, Russell R. Bakken, Michael Hust, Philippe Thullier, John M. Dye

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Marburg virus (MARV) and Ebola virus (EBOV) have been a source of epidemics and outbreaks for several decades. We present here the generation and characterization of the first protective antibodies specific for wild-type MARV. Non-human primates (NHP), cynomolgus macaques, were immunized with viral-replicon particles expressing the glycoproteins (GP) of MARV (Ci67 isolate). An antibody fragment (single-chain variable fragment, scFv) phage display library was built after four immunogen injections, and screened against the GP1-649 of MARV. Sequencing of 192 selected clones identified 18 clones with distinct VH and VL sequences. Four of these recombinant antibodies (R4A1, R4B11, R4G2, and R3F6) were produced in the scFv-Fc format for in vivo studies. Mice that were challenged with wild-type Marburg virus (Ci67 isolate) receiving 100 µg of scFv-Fc on days −1, 1 and 3 demonstrated protective efficacies ranging from 75–100%. The amino-acid sequences of the scFv-Fcs are similar to those of their human germline counterparts, sharing an identity ranging between 68 and 100% to human germline immunoglobulin. These results demonstrate for the first time that recombinant antibodies offer protection against wild-type MARV, and suggest they may be promising candidates for further therapeutic development especially due to their human homology.

Original languageEnglish (US)
Pages (from-to)696-703
Number of pages8
JournalmAbs
Volume9
Issue number4
DOIs
StatePublished - May 19 2017

Fingerprint

Marburgvirus
Antibodies
Clone Cells
Ebolavirus
Single-Chain Antibodies
Immunoglobulin Fragments
Replicon
Macaca
Virion
Bacteriophages
Primates
Libraries
Disease Outbreaks
Immunoglobulins
Amino Acid Sequence
Glycoproteins
Injections

Keywords

  • Antibody
  • biodefense
  • ebola
  • filovirus
  • hemorrhagic
  • Marburg
  • murine
  • protection
  • therapeutic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Froude, J. W., Pelat, T., Miethe, S., Zak, S. E., Wec, A. Z., Chandran, K., ... Dye, J. M. (2017). Generation and characterization of protective antibodies to Marburg virus. mAbs, 9(4), 696-703. https://doi.org/10.1080/19420862.2017.1299848

Generation and characterization of protective antibodies to Marburg virus. / Froude, Jeffrey W.; Pelat, Thibaut; Miethe, Sebastian; Zak, Samantha E.; Wec, Anna Z.; Chandran, Kartik; Brannan, Jennifer Mary; Bakken, Russell R.; Hust, Michael; Thullier, Philippe; Dye, John M.

In: mAbs, Vol. 9, No. 4, 19.05.2017, p. 696-703.

Research output: Contribution to journalArticle

Froude, JW, Pelat, T, Miethe, S, Zak, SE, Wec, AZ, Chandran, K, Brannan, JM, Bakken, RR, Hust, M, Thullier, P & Dye, JM 2017, 'Generation and characterization of protective antibodies to Marburg virus', mAbs, vol. 9, no. 4, pp. 696-703. https://doi.org/10.1080/19420862.2017.1299848
Froude, Jeffrey W. ; Pelat, Thibaut ; Miethe, Sebastian ; Zak, Samantha E. ; Wec, Anna Z. ; Chandran, Kartik ; Brannan, Jennifer Mary ; Bakken, Russell R. ; Hust, Michael ; Thullier, Philippe ; Dye, John M. / Generation and characterization of protective antibodies to Marburg virus. In: mAbs. 2017 ; Vol. 9, No. 4. pp. 696-703.
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