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

doi:10.1371/journal.ppat.1005016

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

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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 language	English (US)
Article number	e1005016
Journal	PLoS pathogens
Volume	11
Issue number	6
DOIs	https://doi.org/10.1371/journal.ppat.1005016
State	Published - Jun 1 2015
Externally published	Yes

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Molecular Biology
Genetics
Virology

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Fusco, M. L., Hashiguchi, T., Cassan, R., Biggins, J. E., Murin, C. D., Warfield, K. L., Li, S., Holtsberg, F. W., Shulenin, S., Vu, H., Olinger, G. G., Kim, D. H., Whaley, K. J., Zeitlin, L., Ward, A. B., Nykiforuk, C., Aman, M. J., Berry, J., & Saphire, E. O. (2015). Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs. PLoS pathogens, 11(6), Article e1005016. https://doi.org/10.1371/journal.ppat.1005016

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

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

Abstract

ASJC Scopus subject areas

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