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Mapping Epitopes of Pan‐Ebolavirus Antibodies From Human Survivors
Author(s) -
David Joshua A,
Murin Charles D,
Flyak Andrew,
Turner Hannah L,
Fusco Marnie L,
Saphire Erica Ollmann,
Crowe James E,
Ward Andrew B
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1103.2
Subject(s) - ebolavirus , virology , epitope , antibody , ebola virus , neutralization , biology , cross reactivity , immunology , virus , cross reactions
Members of the Ebolavirus genus including Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV) and Budibugyo ebolavirus (BDBV) cause viral hemorrhagic fever and have high case fatality rates. The current outbreak in Western Africa is the largest on record and has infected over 28,000 individuals, yet no currently approved vaccines or therapeutics exist. Previous reports have revealed that ZMapp™, a cocktail of three antibodies that target the glycoprotein (GP) of EBOV, can revert an active infection in nonhuman primates. A group of recently identified antibodies from human survivors of BDBV and EBOV infections were shown to neutralize their respective virus. Some of the BDBV antibodies were also shown to be cross‐reactive against SUDV and EBOV; however, the basis of cross‐reactivity remains unknown. Here we report single‐particle negative stain EM reconstructions of each antibody in complex with GP. The cross‐reactive antibodies have overlapping epitopes and bind at the top of GP in a subdomain termed the glycan cap which contains multiple N‐linked glycosylation sites. Interestingly, many BDBV‐specific and EBOV‐specific antibodies bind in very close proximity. Therefore, the glycan cap contains structural motifs that influence species cross‐reactivity and neutralization potential of targeting antibodies. Higher resolution structures of these antibodies will be valuable for understanding the details of this important site of vulnerability. Support or Funding Information This work was supported by NIAID Center for Excellence in Translational Research Grant U19AI109762 (to E.O.S., and A.B.W.). J.A.D. was supported by The Scripps Research Institute Summer Undergraduate Research Fellowship Program.