Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 218, Issue -, Pages S528-S536Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiy333
Keywords
Ad5 immunization; cynomolgus macaques; ebolavirus; NPC1; receptor binding domain
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Funding
- Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases
- Frederick National Laboratory for Cancer Research, National Institutes of Health (NIH) [HHSN261200800001E]
- Leidos Biomedical Research, Inc.
- Boston Children's Hospital Faculty Development Award
- [NIH-5K08AI079381]
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We recently identified a single potently neutralizing monoclonal antibody (mAb), mAb114, isolated from a human survivor of natural Zaire ebolavirus (EBOV) infection, which fully protects nonhuman primates (NHPs) against lethal EBOV challenge. To evaluate the ability of vaccination to generate mAbs such as mAb114, we cloned antibodies from NHPs vaccinated with vectors encoding the EBOV glycoprotein (GP). We identified 14 unique mAbs with potent binding to GP, 4 of which were neutralized and had the functional characteristics of mAb114. These vaccine-induced macaque mAbs share many sequence similarities with mAb114 and use the same mAb114 VH gene (ie, IGHV3-13) when classified using the macaque IMGT database. The antigen-specific VH-gene repertoire present after each immunization indicated that IGHV3-13 mAbs populate an EBOV-specific B-cell repertoire that appears to become more prominent with subsequent boosting. These findings will support structure-based vaccine design aimed at enhanced induction of antibodies such as mAb114.
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