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

• DOI: 10.1371/journal.ppat.1005016
• Publication Date: 2015-06-26T18:22:28Z
• Authors: Marnie L. Fusco; Takao Hashiguchi; Robyn Cassan; Julia E. Biggins; Charles D. Murin; Kelly L. Warfield; Sheng Li; Frederick W. Holt...; 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 Sap...
• Keywords: Male; Mice, Inbred BALB C; 0303 health sciences; QH301-705.5; Antibodies, Monoclonal; RC581-607; Cross Reactions; Hemorrhagic Fever, Ebola; Antibodies, Viral; Ebolavirus; 3. Good health; 03 medical and health sciences; Marburgvirus; Animals; Female; Immunization; Marburg Virus Disease; Immunologic diseases. Allergy; Biology (General); Research Article

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.