Viruses 2018, 10(6), 286; https://doi.org/10.3390/v10060286
Post-Exposure Protection in Mice against Sudan Virus by a Two Antibody Cocktail
Jeffrey W. Froude 1,*,†, Andrew S. Herbert 1, Thibaut Pelat 2, Sebastian Miethe 3, Samantha E. Zak 1, Jennifer M. Brannan 1, Russell R. Bakken 1, Alexander R. Steiner 4, Gang Yin 4, Trevor J. Hallam 4, Aaron K. Sato 4,‡, Michael Hust 3
, Philippe Thullier 2 and John M. Dye 1,*
, Philippe Thullier 2 and John M. Dye 1,*
1
US Army Medical Research Institute for Infectious Disease (USAMRIID), Fort Detrick, MD 21702, USA
2
Unite de Biotechnologie des Anticorps, Institut de Recherche Biomedicale des Armees (IRBA-CRSSA), La Tronche 38516, France
3
Institut für Biochemie, Biotechnologie und Bioinformatik, Technische Universität Braunschweig, Braunschweig 38106, Germany
4
Sutro Biopharma Inc., South San Francisco, CA 94080, USA
*
Authors to whom correspondence should be addressed.
â€
Currently working at Vaccines and Therapeutics Division of the Defense Threat Reduction Agency (DTRA), Fort Belvoir, VA 22060, USA.
‡
Currently working at LakePharma Inc., South San Francisco, CA 24080, USA.
Received: 18 April 2018 / Revised: 18 May 2018 / Accepted: 24 May 2018 / Published: 26 May 2018
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
Abstract
Sudan virus (SUDV) and Ebola viruses (EBOV) are both members of the Ebolavirus genus and have been sources of epidemics and outbreaks for several decades. We present here the generation and characterization of cross-reactive antibodies to both SUDV and EBOV, which were produced in a cell-free system and protective against SUDV in mice. A non-human primate, cynomolgus macaque, was immunized with viral-replicon particles expressing the glycoprotein of SUDV-Boniface (8A). Two separate antibody fragment phage display libraries were constructed after four immunogen injections. Both libraries were screened first against the SUDV and a second library was cross-selected against EBOV-Kikwit. Sequencing of 288 selected clones from the two distinct libraries identified 58 clones with distinct VH and VL sequences. Many of these clones were cross-reactive to EBOV and SUDV and able to neutralize SUDV. Three of these recombinant antibodies (X10B1, X10F3, and X10H2) were produced in the scFv-Fc format utilizing a cell-free production system. Mice that were challenged with SUDV-Boniface receiving 100µg of the X10B1/X10H2 scFv-Fc combination 6 and 48-h post-exposure demonstrated partial protection individually and complete protection as a combination. The data herein suggests these antibodies may be promising candidates for further therapeutic development. View Full-TextKeywords:
Sudan virus; Ebola; antibody; protection; biodefense; cell-free production; phage display
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MDPI and ACS Style
Froude, J.W.; Herbert, A.S.; Pelat, T.; Miethe, S.; Zak, S.E.; Brannan, J.M.; Bakken, R.R.; Steiner, A.R.; Yin, G.; Hallam, T.J.; Sato, A.K.; Hust, M.; Thullier, P.; Dye, J.M. Post-Exposure Protection in Mice against Sudan Virus by a Two Antibody Cocktail. Viruses 2018, 10, 286.
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