Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs

Marnie L. Fusco, Takao Hashiguchi, Robyn Cassan, Julia E. Biggins, Charles D. Murin, Kelly L. Warfield, Sheng Li, Frederick W. Holtsberg, Sergey Shulenin, Hong Vu, Gene G. Olinger, Do H. Kim, Kevin J. Whaley, Larry Zeitlin, Andrew B. Ward, Cory Nykiforuk, M. Javad Aman, Jody Berry, Erica Ollmann Saphire

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.

Original languageEnglish
Article numbere1005016
JournalPLoS pathogens
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Marburgvirus
Ebolavirus
Immunization
Mucins
Monoclonal Antibodies
Glycoproteins
Sudan
Antibodies
Membrane Glycoproteins
Primates
Disease Outbreaks
Epitopes
Anti-Idiotypic Antibodies
Viruses

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Fusco, M. L., Hashiguchi, T., Cassan, R., Biggins, J. E., Murin, C. D., Warfield, K. L., ... Saphire, E. O. (2015). Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs. PLoS pathogens, 11(6), [e1005016]. https://doi.org/10.1371/journal.ppat.1005016

Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs. / Fusco, Marnie L.; Hashiguchi, Takao; Cassan, Robyn; Biggins, Julia E.; Murin, Charles D.; Warfield, Kelly L.; Li, Sheng; Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Olinger, Gene G.; Kim, Do H.; Whaley, Kevin J.; Zeitlin, Larry; Ward, Andrew B.; Nykiforuk, Cory; Aman, M. Javad; Berry, Jody; Saphire, Erica Ollmann.

In: PLoS pathogens, Vol. 11, No. 6, e1005016, 01.06.2015.

Research output: Contribution to journalArticle

Fusco, ML, Hashiguchi, T, Cassan, R, Biggins, JE, Murin, CD, Warfield, KL, Li, S, Holtsberg, FW, Shulenin, S, Vu, H, Olinger, GG, Kim, DH, Whaley, KJ, Zeitlin, L, Ward, AB, Nykiforuk, C, Aman, MJ, Berry, J & Saphire, EO 2015, 'Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs', PLoS pathogens, vol. 11, no. 6, e1005016. https://doi.org/10.1371/journal.ppat.1005016
Fusco, Marnie L. ; Hashiguchi, Takao ; Cassan, Robyn ; Biggins, Julia E. ; Murin, Charles D. ; Warfield, Kelly L. ; Li, Sheng ; Holtsberg, Frederick W. ; Shulenin, Sergey ; Vu, Hong ; Olinger, Gene G. ; Kim, Do H. ; Whaley, Kevin J. ; Zeitlin, Larry ; Ward, Andrew B. ; Nykiforuk, Cory ; Aman, M. Javad ; Berry, Jody ; Saphire, Erica Ollmann. / Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs. In: PLoS pathogens. 2015 ; Vol. 11, No. 6.
@article{71b2fce7fef14b4da397928c1724f612,
title = "Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs",
abstract = "The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100{\%} protection, respectively, one hour post-exposure in mice challenged with MARV.",
author = "Fusco, {Marnie L.} and Takao Hashiguchi and Robyn Cassan and Biggins, {Julia E.} and Murin, {Charles D.} and Warfield, {Kelly L.} and Sheng Li and Holtsberg, {Frederick W.} and Sergey Shulenin and Hong Vu and Olinger, {Gene G.} and Kim, {Do H.} and Whaley, {Kevin J.} and Larry Zeitlin and Ward, {Andrew B.} and Cory Nykiforuk and Aman, {M. Javad} and Jody Berry and Saphire, {Erica Ollmann}",
year = "2015",
month = "6",
day = "1",
doi = "10.1371/journal.ppat.1005016",
language = "English",
volume = "11",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs

AU - Fusco, Marnie L.

AU - Hashiguchi, Takao

AU - Cassan, Robyn

AU - Biggins, Julia E.

AU - Murin, Charles D.

AU - Warfield, Kelly L.

AU - Li, Sheng

AU - Holtsberg, Frederick W.

AU - Shulenin, Sergey

AU - Vu, Hong

AU - Olinger, Gene G.

AU - Kim, Do H.

AU - Whaley, Kevin J.

AU - Zeitlin, Larry

AU - Ward, Andrew B.

AU - Nykiforuk, Cory

AU - Aman, M. Javad

AU - Berry, Jody

AU - Saphire, Erica Ollmann

PY - 2015/6/1

Y1 - 2015/6/1

N2 - The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.

AB - The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.

UR - http://www.scopus.com/inward/record.url?scp=84936758666&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84936758666&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1005016

DO - 10.1371/journal.ppat.1005016

M3 - Article

C2 - 26115029

AN - SCOPUS:84936758666

VL - 11

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 6

M1 - e1005016

ER -