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PLoS Pathog. 2015 Jun 26;11(6):e1005016. doi: 10.1371/journal.ppat.1005016. eCollection 2015 Jun.

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

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
2
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America; Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
3
Emergent BioSolutions (formerly Cangene Corporation), Winnipeg, Manitoba, Canada.
4
Division of Virology, United States Army Research Institute for Infectious Disease, Ft. Detrick, Maryland, United States of America; Integrated Biotherapeutics, Inc., Gaithersburg, Maryland, United States of America.
5
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
6
Integrated Biotherapeutics, Inc., Gaithersburg, Maryland, United States of America.
7
Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
8
Division of Virology, United States Army Research Institute for Infectious Disease, Ft. Detrick, Maryland, United States of America; Integrated Research Facility, NIAID, National Institutes of Health, Frederick, Maryland, United States of America.
9
Mapp Biopharmaceutical, Inc., San Diego, California, United States of America.
10
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
11
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America.

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.

PMID:
26115029
PMCID:
PMC4482612
DOI:
10.1371/journal.ppat.1005016
[Indexed for MEDLINE]
Free PMC Article

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